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Recently, we identified LSMEM2, a novel substrate of AMPK in the heart. LSMEM2 is a membrane protein localized at the intercalated disc (ICD), whose function is currently under investigation. Interestingly, LSMEM2 is also expressed in the skeletal muscles. As skeletal muscles lack a homophilic intercellular junction corresponding to the ICD in the heart, predicting the role of LSMEM2 in skeletal muscles is difficult. In this study, we identified that LSMEM2 is expressed in skeletal muscles, specifically at the neuromuscular junction (NMJ). LSMEM2\u2010knockout mice showed no histological abnormalities, suggesting that LSMEM2 is not essential for skeletal muscle development. The overexpression of full\u2010length wild\u2010type or C\u2010del mutant of LSMEM2 led to the tubular aggregate formation with functional abnormality in male mice. RNA sequence analysis revealed that the gene sets of mitochondrial oxidative phosphorylation and vesicle\u2010mediated transport are enriched in LSMEM2 overexpression. Furthermore, histological analysis demonstrated the accumulation of swollen subsarcolemmal mitochondria in LSMEM2\u2010overexpressing skeletal muscles. The study findings suggest that LSMEM2 may play a role in the pathogenesis of skeletal muscle diseases.<\/jats:p>","DOI":"10.1096\/fj.202402152r","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T08:53:14Z","timestamp":1750150394000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>LSMEM2<\/scp>\n                    , Localized at the Neuromuscular Junction, Modulates Mitochondrial Integration in Skeletal Muscles"],"prefix":"10.1096","volume":"39","author":[{"given":"Eman","family":"Elrefaei","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmacology National Cerebral and Cardiovascular Center  Suita Osaka Japan"},{"name":"Department of Medical Biochemistry Osaka University Graduate School of Medicine  Suita Osaka Japan"},{"name":"Department of Medical Biochemistry Faculty of Medicine, Tanta University  Tanta 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