{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNHLRC1 encodes the protein known as malin, a RING‐finger E3 ubiquitin ligase characterized by six NHL repeats. Malin forms a functional complex with the glucan phosphatase laforin, and together they target specific substrates for ubiquitination and proteasomal degradation. This process is fundamental for preventing the accumulation of insoluble polyglucosans (Lafora bodies) in neurons and other tissues, a hallmark of Lafora disease. In cellular systems, malin promotes the turnover of laforin as well as other regulators of glycogen synthesis, thus maintaining proper glycogen homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nThrough its enzymatic activity, malin exerts tight control over glycogen metabolism by targeting key substrates. For instance, it ubiquitinates regulatory proteins such as the glycogen-targeting subunit R5/PTG—whose phosphorylation by AMP-activated protein kinase (AMPK) facilitates its degradation—as well as neuronatin, thereby suppressing aberrant glycogen synthesis. In addition, malin can negatively regulate elements of signal transduction pathways (e.g. by promoting the degradation of dishevelled2, a mediator of Wnt signaling). These coordinated events are critical to preventing the formation of less-branched, insoluble glycogen inclusions."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in glycogen regulation, malin plays multifaceted roles in protein quality control and stress responses. Under conditions of proteasomal stress, malin (together with laforin) is recruited to aggresome-like structures where it collaborates with molecular chaperones to clear misfolded proteins. Moreover, malin mediates the ubiquitination of key metabolic regulators such as AMPK, thereby influencing cellular energy sensing. It also localizes to processing bodies to control mRNA decay and interacts with components of the autophagic machinery—through associations with the phosphatidylinositol-3 kinase complex—to facilitate autophagosome formation. Reciprocal regulation between malin and laforin further fine-tunes these degradation pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nExtensive genetic and clinical investigations have documented a wide spectrum of NHLRC1 (malin) mutations that undermine its ubiquitin ligase activity. These mutations disrupt the degradation of substrates essential for glycogen turnover and protein clearance, thereby precipitating the neurodegenerative manifestations of Lafora disease. Comparative studies across diverse populations—as well as evolutionary and subcellular localization analyses—underscore not only the critical regulatory roles of malin but also the clinical heterogeneity observed in affected individuals."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "32"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elayne M Chan, Edwin J Young, Leonarda Ianzano, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Regulation of glycogen synthesis by the laforin-malin complex is modulated by the AMP-activated protein kinase pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm339"}], "href": "https://doi.org/10.1093/hmg/ddm339"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18029386"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18029386"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Carolyn A Worby, Matthew S Gentry, Jack E Dixon "}, {"type": "b", "children": [{"type": "t", "text": "Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M708712200"}], "href": "https://doi.org/10.1074/jbc.M708712200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18070875"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18070875"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Santiago Vernia, M Carmen Solaz-Fuster, José Vicente Gimeno-Alcañiz, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "The malin-laforin complex suppresses the cellular toxicity of misfolded proteins by promoting their degradation through the ubiquitin-proteasome system."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddn398"}], "href": "https://doi.org/10.1093/hmg/ddn398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19036738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19036738"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Santiago Vernia, Teresa Rubio, Miguel Heredia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased endoplasmic reticulum stress and decreased proteasomal function in lafora disease models lacking the phosphatase laforin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0005907"}], "href": "https://doi.org/10.1371/journal.pone.0005907"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19529779"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19529779"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Sudheendra N R Rao, Jaiprakash Sharma, Ranjan Maity, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Co-chaperone CHIP stabilizes aggregate-prone malin, a ubiquitin ligase mutated in Lafora disease."}]}, {"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.M109.006312"}], "href": "https://doi.org/10.1074/jbc.M109.006312"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19892702"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19892702"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Daniel Moreno, Mhairi C Towler, D Grahame Hardie, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Interdependence of laforin and malin proteins for their stability and functions could underlie the molecular basis of locus heterogeneity in Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biosci (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12038-015-9570-0"}], "href": "https://doi.org/10.1007/s12038-015-9570-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26648032"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26648032"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Pablo Sanchez-Martin, Marcos Lahuerta, Rosa Viana, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the autophagic PI3KC3 complex by laforin/malin E3-ubiquitin ligase, two proteins involved in Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbamcr.2019.118613"}], "href": "https://doi.org/10.1016/j.bbamcr.2019.118613"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31758957"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31758957"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "C Gómez-Abad, P Gómez-Garre, E Gutiérrez-Delicado, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lafora disease due to EPM2B mutations: a clinical and genetic study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurology (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1212/01.WNL.0000154519.10805.F7"}], "href": "https://doi.org/10.1212/01.WNL.0000154519.10805.F7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15781812"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15781812"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "S Singh, I Sethi, S Francheschetti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel NHLRC1 mutations and genotype-phenotype correlations in patients with Lafora's progressive myoclonic epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2005.039479"}], "href": "https://doi.org/10.1136/jmg.2005.039479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16950819"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16950819"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Shweta Singh, Parthasarathy Satishchandra, Susarla Krishna Shankar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lafora disease in the Indian population: EPM2A and NHLRC1 gene mutations and their impact on subcellular localization of laforin and malin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20737"}], "href": "https://doi.org/10.1002/humu.20737"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18311786"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18311786"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Shweta Singh, Subramaniam Ganesh "}, {"type": "b", "children": [{"type": "t", "text": "Lafora progressive myoclonus epilepsy: a meta-analysis of reported mutations in the first decade following the discovery of the EPM2A and NHLRC1 genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mutat (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/humu.20954"}], "href": "https://doi.org/10.1002/humu.20954"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19267391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19267391"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "M Traoré, G Landouré, W Motley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neurogenetics (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10048-009-0190-4"}], "href": "https://doi.org/10.1007/s10048-009-0190-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19322595"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19322595"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Gaetan Lesca, Nadia Boutry-Kryza, Bertrand de Toffol, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel mutations in EPM2A and NHLRC1 widen the spectrum of Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1528-1167.2010.02692.x"}], "href": "https://doi.org/10.1111/j.1528-1167.2010.02692.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20738377"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20738377"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Carlos Romá-Mateo, Daniel Moreno, Santiago Vernia, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lafora disease E3-ubiquitin ligase malin is related to TRIM32 at both the phylogenetic and functional level."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Evol Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2148-11-225"}], "href": "https://doi.org/10.1186/1471-2148-11-225"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21798009"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21798009"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Seda Salar, Naz Yeni, Ayşegül Gündüz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Four novel and two recurrent NHLRC1 (EPM2B) and EPM2A gene mutations leading to Lafora disease in six Turkish families."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsy Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.eplepsyres.2011.09.020"}], "href": "https://doi.org/10.1016/j.eplepsyres.2011.09.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22047982"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22047982"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "Edoardo Ferlazzo, Laura Canafoglia, Roberto Michelucci, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mild Lafora disease: clinical, neurophysiologic, and genetic findings."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epilepsia (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/epi.12806"}], "href": "https://doi.org/10.1111/epi.12806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25270369"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25270369"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Rosa Viana, Pablo Lujan, Pascual Sanz "}, {"type": "b", "children": [{"type": "t", "text": "The laforin/malin E3-ubiquitin ligase complex ubiquitinates pyruvate kinase M1/M2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Biochem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12858-015-0053-6"}], "href": "https://doi.org/10.1186/s12858-015-0053-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26493215"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26493215"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Garen Haryanyan, Ozkan Ozdemir, Kemal Tutkavul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The rare rs769301934 variant in NHLRC1 is a common cause of Lafora disease in Turkey."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-021-00944-8"}], "href": "https://doi.org/10.1038/s10038-021-00944-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34117373"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34117373"}]}, {"type": "r", "ref": 31, "children": [{"type": "t", "text": "Xinghua Tang, Xinjuan Li, Yuncan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Compound heterozygosity for novel variations of the NHLRC1 Gene in a family with Lafora disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Neurol Neurosurg (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clineuro.2022.107255"}], "href": "https://doi.org/10.1016/j.clineuro.2022.107255"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35569391"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35569391"}]}, {"type": "r", "ref": 32, "children": [{"type": "t", "text": "Christian Faltus, Angelika Lahnsteiner, Myrto Barrdahl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "NHLRC1"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " as a Novel AKT Activator from a Lung Cancer Epigenome-Wide Association Study (EWAS)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Mol Sci (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/ijms231810699"}], "href": "https://doi.org/10.3390/ijms231810699"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36142605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36142605"}]}]}]}