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Loss or dysfunction of skeletal muscle caveolae can cause a spectrum of muscle diseases, including caveolinopathies associated with rippling muscle disease. Despite recent advances, the precise downstream mechanisms that link caveolar defects to muscle dysfunction are not resolved. In this review, we discuss the fundamental cell biology underpinning muscle diseases associated with caveolar disruption. We highlight how recent structural and functional advances in both muscle and non-muscle systems are providing crucial insights into these pathological processes. Specifically, we analyze how the loss of these abundant surface domains disrupts mechanoprotection, signal transduction, nanoscale lipid organization, and T-tubule biogenesis and function. Finally, we propose a unifying cell biological classification system for disease-associated variants of caveolin-3, with a view to providing a mechanistic framework to connect molecular defects with clinical phenotypes.<\/jats:p>","DOI":"10.1083\/jcb.202605101","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:21:04Z","timestamp":1786429264000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Dysfunction of caveolae in muscle disease: A cell biological perspective"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3998-6132","authenticated-orcid":true,"given":"Harriet P.","family":"Lo","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00rqy9422","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Molecular Bioscience, The University of Queensland 1 , St Lucia,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0172-330X","authenticated-orcid":true,"given":"St\u00e9phane","family":"Vassilopoulos","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02e3eqz10","id-type":"ROR","asserted-by":"publisher"}],"name":"Myology Research Center\/Institute of Myology, UMRS 974 Sorbonne University-Inserm, G.H. 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