{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nA number of recent studies have dissected the molecular mechanisms underpinning diverse biological processes including spermatogenesis, epithelial barrier formation, and metabolic as well as genome‐regulatory functions. For example, investigations of gene expression in mouse spermatogonia have emphasized the importance of X‐linked genes and the complex orchestration of pre‐ and post‐meiotic events ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "]. In parallel, detailed examinations of tight junction components and MARVEL‐domain proteins in epithelia have revealed overlapping as well as unique roles in cell polarity and barrier regulation ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nOther studies have focused on post‐translational regulation mechanisms. For instance, several reports have detailed how deubiquitinating enzymes (such as USP26 and USP29) and protein deacetylases contribute to the regulation of glucokinase activity in liver metabolism, the stability of key regulatory proteins during cell cycle and chromosomal dynamics, and the coordination of bone homeostasis ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "13"}]}, {"type": "t", "text": "]. Similarly, the interplay between proteins involved in chromosomal cohesion and epigenetic silencing—such as the PDS5 proteins and components of Polycomb complexes—has been shown to be essential for proper genome organization and developmental regulation ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "17"}]}, {"type": "t", "text": "].\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNotably, despite the wide range of cellular processes and regulatory networks elucidated by these studies—from reproductive cell biology and tight junction dynamics to metabolic control and chromosomal regulation—not a single report has addressed the biological function or signaling role of OR2H1. In other words, while these works collectively advance our understanding of gene regulation and protein function in key physiological and pathological contexts, none provide any direct or indirect insight into OR2H1’s role. Future targeted research will be necessary to determine whether OR2H1 participates in any of these pathways or contributes to related disease phenotypes ["}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "23"}]}, {"type": "t", "text": "].\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "P J Wang, J R McCarrey, F Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An abundance of X-linked genes expressed in spermatogonia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/86927"}], "href": "https://doi.org/10.1038/86927"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11279525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11279525"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "P Jeremy Wang, David C Page, John R McCarrey "}, {"type": "b", "children": [{"type": "t", "text": "Differential expression of sex-linked and autosomal germ-cell-specific genes during spermatogenesis in the mouse."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddi322"}], "href": "https://doi.org/10.1093/hmg/ddi322"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16118233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16118233"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nives Zimmermann, Matthew P Doepker, David P Witte, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Usp26 mutation in mice leads to defective spermatogenesis depending on genetic background."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-50318-6"}], "href": "https://doi.org/10.1038/s41598-019-50318-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31551464"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31551464"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Chao Liu, Hongbin Liu, Haobo Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Paternal USP26 mutations raise Klinefelter syndrome risk in the offspring of mice and humans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.2020106864"}], "href": "https://doi.org/10.15252/embj.2020106864"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33978233"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33978233"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "David R Raleigh, Amanda M Marchiando, Yong Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.e09-08-0734"}], "href": "https://doi.org/10.1091/mbc.e09-08-0734"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20164257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20164257"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Charlotte Heymans, Ophélie Delcorte, Catherine Spourquet, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Spatio-temporal expression pattern and role of the tight junction protein MarvelD3 in pancreas development and function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-021-93654-2"}], "href": "https://doi.org/10.1038/s41598-021-93654-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34267243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34267243"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Franziska Weiß, Carolina Czichos, Lukas Knobe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MarvelD3 Is Upregulated in Ulcerative Colitis and Has Attenuating Effects during Colitis Indirectly Stabilizing the Intestinal Barrier."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cells (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3390/cells11091541"}], "href": "https://doi.org/10.3390/cells11091541"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35563847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35563847"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Hitoshi Watanabe, Yuka Inaba, Kumi Kimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sirt2 facilitates hepatic glucose uptake by deacetylating glucokinase regulatory protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-017-02537-6"}], "href": "https://doi.org/10.1038/s41467-017-02537-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29296001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29296001"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Joo-Man Park, Tae-Hyun Kim, Seong-Ho Jo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Acetylation of glucokinase regulatory protein decreases glucose metabolism by suppressing glucokinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep17395"}], "href": "https://doi.org/10.1038/srep17395"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26620281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26620281"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Changwei Li, Minglong Qiu, Leilei Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The osteoprotective role of USP26 in coordinating bone formation and resorption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Differ (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41418-021-00904-x"}], "href": "https://doi.org/10.1038/s41418-021-00904-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35091692"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35091692"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Alberto Viera, Inés Berenguer, Miguel Ruiz-Torres, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PDS5 proteins regulate the length of axial elements and telomere integrity during male mouse meiosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embr.201949273"}], "href": "https://doi.org/10.15252/embr.201949273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32285610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32285610"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Hong Tian, Yongwei Huo, Jie Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of ubiquitin specific protease 26 gene causes male subfertility associated with spermatogenesis defects in mice†."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/biolre/ioy258"}], "href": "https://doi.org/10.1093/biolre/ioy258"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30561524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30561524"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bin Zhang, Jufang Chang, Ming Fu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dosage effects of cohesin regulatory factor PDS5 on mammalian development: implications for cohesinopathies."}]}, {"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.0005232"}], "href": "https://doi.org/10.1371/journal.pone.0005232"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19412548"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19412548"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Daniel Bsteh, Hagar F Moussa, Georg Michlits, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-023-43869-w"}], "href": "https://doi.org/10.1038/s41467-023-43869-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38071364"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38071364"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Nicole L Arruda, Audra F Bryan, Jill M Dowen "}, {"type": "b", "children": [{"type": "t", "text": "PDS5A and PDS5B differentially affect gene expression without altering cohesin localization across the genome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Epigenetics Chromatin (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13072-022-00463-6"}], "href": "https://doi.org/10.1186/s13072-022-00463-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35986423"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35986423"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Mengru Ma, Lian Yi, Yifei Pei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-024-52201-z"}], "href": "https://doi.org/10.1038/s41467-024-52201-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39251623"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39251623"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Joseph P McElroy, Bruce A C Cree, Stacy J Caillier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Refining the association of MHC with multiple sclerosis in African Americans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddq197"}], "href": "https://doi.org/10.1093/hmg/ddq197"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20466734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20466734"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Y-W Lin, T-H Hsu, P H Yen "}, {"type": "b", "children": [{"type": "t", "text": "Localization of ubiquitin specific protease 26 at blood-testis barrier and near Sertoli cell-germ cell interface in mouse testes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Androl (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2605.2010.01130.x"}], "href": "https://doi.org/10.1111/j.1365-2605.2010.01130.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21449984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21449984"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Jia-Bao Hou, Qian-Ni Shen, Xing Wan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ubiquitin-Specific Protease 29 Exacerbates Cerebral Ischemia-Reperfusion Injury in Mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oxid Med Cell Longev (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2021/6955628"}], "href": "https://doi.org/10.1155/2021/6955628"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34824671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34824671"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Brian E Ford, Shruti S Chachra, Katrina Rodgers, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Hepatic glucokinase regulatory protein and carbohydrate response element binding protein attenuation reduce de novo lipogenesis but do not mitigate intrahepatic triglyceride accumulation in Aldob deficiency."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Metab (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmet.2024.101984"}], "href": "https://doi.org/10.1016/j.molmet.2024.101984"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38972375"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38972375"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Anna Segarra-Fas, Carmen Espejo-Serrano, Francisco Bustos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "An RNF12-USP26 amplification loop drives germ cell specification and is disrupted by disease-associated mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Signal (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/scisignal.abm5995"}], "href": "https://doi.org/10.1126/scisignal.abm5995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35857630"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35857630"}]}]}]}