{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAcid sphingomyelinase (ASMase), the enzyme encoded by SMPD1, is a key mediator that hydrolyzes sphingomyelin into ceramide – a bioactive lipid with numerous signaling functions. In the central nervous system its activation promotes glial microparticle shedding and interleukin‑1β release, thereby contributing to neuroinflammatory‐mediated events. In parallel, modulation of ASMase activity influences neurogenesis and mood regulation in major depression, while increased enzyme activity—as observed in Alzheimer’s disease—impairs autophagic degradation and may exacerbate neurodegeneration. In the skin, reduced ASMase and consequent ceramide deficiency correlate with defective barrier formation in atopic dermatitis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its homeostatic roles, ASMase is mobilized in response to external stress and infection. Upon exposure to pathogens such as rhinoviruses, Ebola virus, and meningococci, ASMase rapidly translocates to the plasma membrane where its generation of ceramide promotes the formation of ceramide‐enriched platforms that facilitate microbial uptake. Similarly, ultraviolet irradiation and chemotherapeutic agents like cisplatin trigger ASMase activation, leading to ceramide accumulation and initiation of apoptosis via mitochondrial and death receptor pathways. In these contexts the enzyme’s activity is regulated by post‐translational events (including phosphorylation and lysosomal exocytosis) as well as secretion in response to inflammatory cytokines, thereby linking its function to host defense and programmed cell death."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic and regulatory studies further underscore the clinical significance of SMPD1. Mutations in the gene cause Niemann–Pick disease types A and B and have been associated with an increased risk of Parkinson’s disease, as demonstrated by studies in diverse populations. Detailed biochemical investigations have elucidated regulatory mechanisms—including post‑translational modifications of the C‑terminal cysteine, transcriptional control by retinoids, and lysosomal targeting via sortilin—that fine‑tune ASMase activity. Moreover, altered SMPD1 expression has been linked not only to inflammatory conditions such as sepsis and chronic liver disease but also to tumor biology, where ASMase–mediated ceramide production can determine the balance between cell survival and apoptosis in cancers like non–small cell lung cancer and melanoma. Collectively, these findings establish ASMase as a central node integrating stress responses, immune signaling, and cell fate decisions, and they highlight its potential as a target for therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "34"}, {"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fabio Bianco, Cristiana Perrotta, Luisa Novellino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase activity triggers microparticle release from glial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2009.45"}], "href": "https://doi.org/10.1038/emboj.2009.45"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19300439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19300439"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Erich Gulbins, Monica Palmada, Martin Reichel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.3214"}], "href": "https://doi.org/10.1038/nm.3214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23770692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23770692"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jens-Michael Jensen, Regina Fölster-Holst, Anke Baranowsky, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.0022-202X.2004.22621.x"}], "href": "https://doi.org/10.1111/j.0022-202X.2004.22621.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15175033"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15175033"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jong Kil Lee, Hee Kyung Jin, Min Hee Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase modulates the autophagic process by controlling lysosomal biogenesis in Alzheimer's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20132451"}], "href": "https://doi.org/10.1084/jem.20132451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25049335"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25049335"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Heike Grassmé, Andrea Riehle, Barbara Wilker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M500835200"}], "href": "https://doi.org/10.1074/jbc.M500835200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15888438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15888438"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jimmy A Rotolo, Jianjun Zhang, Manjula Donepudi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Caspase-dependent and -independent activation of acid sphingomyelinase signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M414569200"}], "href": "https://doi.org/10.1074/jbc.M414569200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15849201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15849201"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Youssef H Zeidan, Russell W Jenkins, Yusuf A Hannun "}, {"type": "b", "children": [{"type": "t", "text": "Remodeling of cellular cytoskeleton by the acid sphingomyelinase/ceramide pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200705060"}], "href": "https://doi.org/10.1083/jcb.200705060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18426979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18426979"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Mary E Miller, Shramika Adhikary, Andrey A Kolokoltsov, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ebolavirus requires acid sphingomyelinase activity and plasma membrane sphingomyelin for infection."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.00136-12"}], "href": "https://doi.org/10.1128/JVI.00136-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22573858"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22573858"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Alexei Gorelik, Katalin Illes, Leonhard X Heinz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of mammalian acid sphingomyelinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms12196"}], "href": "https://doi.org/10.1038/ncomms12196"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27435900"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27435900"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Hamid Kashkar, Katja Wiegmann, Benjamin Yazdanpanah, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase is indispensable for UV light-induced Bax conformational change at the mitochondrial membrane."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M410869200"}], "href": "https://doi.org/10.1074/jbc.M410869200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15743760"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15743760"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Russell W Jenkins, Daniel Canals, Jolanta Idkowiak-Baldys, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.125609"}], "href": "https://doi.org/10.1074/jbc.M110.125609"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20807762"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20807762"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Stefania Zampieri, Mirella Filocamo, Annalisa Pianta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SMPD1 Mutation Update: Database and Comprehensive Analysis of Published and Novel Variants."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.22923"}], "href": "https://doi.org/10.1002/humu.22923"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26499107"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26499107"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yan-Feng Zhou, Matthew C Metcalf, Scott C Garman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human acid sphingomyelinase structures provide insight to molecular basis of Niemann-Pick disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms13082"}], "href": "https://doi.org/10.1038/ncomms13082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27725636"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27725636"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Colin Niaudet, Stéphanie Bonnaud, Maëva Guillonneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasma membrane reorganization links acid sphingomyelinase/ceramide to p38 MAPK pathways in endothelial cells apoptosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2017.02.001"}], "href": "https://doi.org/10.1016/j.cellsig.2017.02.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28179144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28179144"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Ziv Gan-Or, Laurie J Ozelius, Anat Bar-Shira, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The p.L302P mutation in the lysosomal enzyme gene SMPD1 is a risk factor for Parkinson disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/WNL.0b013e31828f180e"}], "href": "https://doi.org/10.1212/WNL.0b013e31828f180e"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23535491"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23535491"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Huawei Qiu, Tim Edmunds, Jennifer Baker-Malcolm, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of human acid sphingomyelinase through modification or deletion of C-terminal cysteine."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M303022200"}], "href": "https://doi.org/10.1074/jbc.M303022200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12801930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12801930"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Roy N Alcalay, Victoria Mallett, Benoît Vanderperre, et al. "}, {"type": "b", "children": [{"type": "t", "text": "SMPD1 mutations, activity, and α-synuclein accumulation in Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mov Disord (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/mds.27642"}], "href": "https://doi.org/10.1002/mds.27642"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30788890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30788890"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Jia-Nee Foo, Herty Liany, Jin-Xin Bei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare lysosomal enzyme gene SMPD1 variant (p.R591C) associates with Parkinson's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurobiol Aging (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neurobiolaging.2013.06.010"}], "href": "https://doi.org/10.1016/j.neurobiolaging.2013.06.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23871123"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23871123"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "H Pavlů-Pereira, B Asfaw, H Poupctová, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase deficiency. Phenotype variability with prevalence of intermediate phenotype in a series of twenty-five Czech and Slovak patients. A multi-approach study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-005-5671-5"}], "href": "https://doi.org/10.1007/s10545-005-5671-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15877209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15877209"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Cristiana Perrotta, Davide Cervia, Ilaria Di Renzo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Nitric Oxide Generated by Tumor-Associated Macrophages Is Responsible for Cancer Resistance to Cisplatin and Correlated With Syntaxin 4 and Acid Sphingomyelinase Inhibition."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2018.01186"}], "href": "https://doi.org/10.3389/fimmu.2018.01186"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29896202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29896202"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Antonella Managò, Katrin Anne Becker, Alexander Carpinteiro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pseudomonas aeruginosa pyocyanin induces neutrophil death via mitochondrial reactive oxygen species and mitochondrial acid sphingomyelinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Antioxid Redox Signal (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/ars.2014.5979"}], "href": "https://doi.org/10.1089/ars.2014.5979"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25686490"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25686490"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "J Kornhuber, A Medlin, S Bleich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High activity of acid sphingomyelinase in major depression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neural Transm (Vienna) (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00702-005-0374-5"}], "href": "https://doi.org/10.1007/s00702-005-0374-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16245071"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16245071"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Ralf A Claus, Alexander C Bunck, Clemens L Bockmeyer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of increased sphingomyelinase activity in apoptosis and organ failure of patients with severe sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.04-2842fje"}], "href": "https://doi.org/10.1096/fj.04-2842fje"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16051685"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16051685"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "Xingxuan He, Nozomu Okino, Rajwinder Dhami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Purification and characterization of recombinant, human acid ceramidase. Catalytic reactions and interactions with acid sphingomyelinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M301936200"}], "href": "https://doi.org/10.1074/jbc.M301936200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12815059"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12815059"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Xiaoyan Ni, Carlos R Morales "}, {"type": "b", "children": [{"type": "t", "text": "The lysosomal trafficking of acid sphingomyelinase is mediated by sortilin and mannose 6-phosphate receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2006.00429.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2006.00429.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16787399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16787399"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Marianna Spatola, Christian Wider "}, {"type": "b", "children": [{"type": "t", "text": "Genetics of Parkinson's disease: the yield."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsonism Relat Disord (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S1353-8020(13)70011-7"}], "href": "https://doi.org/10.1016/S1353-8020(13"}, {"type": "t", "text": "70011-7) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24262184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24262184"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Russell W Jenkins, Jolanta Idkowiak-Baldys, Fabio Simbari, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.155234"}], "href": "https://doi.org/10.1074/jbc.M110.155234"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21098024"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21098024"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Georgios Grammatikos, Christiane Mühle, Nerea Ferreiros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum acid sphingomyelinase is upregulated in chronic hepatitis C infection and non alcoholic fatty liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2014.04.007"}], "href": "https://doi.org/10.1016/j.bbalip.2014.04.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24769340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24769340"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "E Dagan, I Schlesinger, M Ayoub, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The contribution of Niemann-Pick SMPD1 mutations to Parkinson disease in Ashkenazi Jews."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Parkinsonism Relat Disord (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.parkreldis.2015.06.016"}], "href": "https://doi.org/10.1016/j.parkreldis.2015.06.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26169695"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26169695"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Takashi Murate, Motoshi Suzuki, Masashi Hattori, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Up-regulation of acid sphingomyelinase during retinoic acid-induced myeloid differentiation of NB4, a human acute promyelocytic leukemia cell line."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111594200"}], "href": "https://doi.org/10.1074/jbc.M111594200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11788605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11788605"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Calogera M Simonaro, Jae-Ho Park, Efrat Eliyahu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Imprinting at the SMPD1 locus: implications for acid sphingomyelinase-deficient Niemann-Pick disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1086/503750"}], "href": "https://doi.org/10.1086/503750"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16642440"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16642440"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "M G Pittis, V Ricci, V I Guerci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase: identification of nine novel mutations among Italian Niemann Pick type B patients and characterization of in vivo functional in-frame start codon."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.9263"}], "href": "https://doi.org/10.1002/humu.9263"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15241805"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15241805"}]}, {"type": "r", "ref": 33, "children": [{"type": "t", "text": "Stephanie Lansmann, Christina G Schuette, Oliver Bartelsen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human acid sphingomyelinase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Biochem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1046/j.1432-1033.2003.03435.x"}], "href": "https://doi.org/10.1046/j.1432-1033.2003.03435.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12631268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12631268"}]}, {"type": "r", "ref": 34, "children": [{"type": "t", "text": "Eric L Smith, Edward H Schuchman "}, {"type": "b", "children": [{"type": "t", "text": "Acid sphingomyelinase overexpression enhances the antineoplastic effects of irradiation in vitro and in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/mt.2008.145"}], "href": "https://doi.org/10.1038/mt.2008.145"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18628757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18628757"}]}]}]}