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A dysfunctional UPS is a hallmark of muscle ageing and is often impacted in neuromuscular disorders (NMDs). Malfunction of the UPS often results in aberrant protein accumulation which can lead to protein aggregation and\/or mis-localization affecting its function. Deubiquitinating enzymes (DUBs) are key players in the UPS, controlling protein turnover and maintaining the free ubiquitin pool. Several mutations in DUB encoding genes are linked to human NMDs, such as ATXN3, OTUD7A, UCHL1 and USP14, whilst other NMDs are associated with dysregulation of DUB expression. USP5, USP9X and USP14 are implicated in synaptic transmission and remodeling at the neuromuscular junction. Mice lacking USP19 show increased maintenance of lean muscle mass. In this review, we highlight the involvement of DUBs in muscle physiology and NMDs, particularly in processes affecting muscle regeneration, degeneration and inflammation following muscle injury. DUBs have recently garnered much respect as promising drug targets, and their roles in muscle maturation, regeneration and degeneration may provide the framework for novel therapeutics to treat muscular disorders including NMDs, sarcopenia and cachexia.<\/jats:p>","DOI":"10.1042\/bst20230562","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T11:24:26Z","timestamp":1715167466000},"page":"1085-1098","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Deubiquitinases in muscle physiology and disorders"],"prefix":"10.1042","volume":"52","author":[{"given":"Cyriel S.","family":"Olie","sequence":"first","affiliation":[{"name":"1Department of Human Genetics, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darragh P.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7834-0625","authenticated-orcid":false,"given":"Hannah B.L.","family":"Jones","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhu","family":"Liang","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."},{"name":"3Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Damianou","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."},{"name":"3Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilknur","family":"Sur-Erdem","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."},{"name":"4Nuffield Department of Women's and Reproductive Health, University of Oxford, Women's Centre, John Radcliffe Hospital, Oxford OX3 9DU, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ad\u00e1n","family":"Pinto-Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."},{"name":"3Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vered","family":"Raz","sequence":"additional","affiliation":[{"name":"1Department of Human Genetics, Leiden University Medical Centre, 2333ZC Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8160-2446","authenticated-orcid":false,"given":"Benedikt M.","family":"Kessler","sequence":"additional","affiliation":[{"name":"2Target Discovery Institute, Centre for Medicines Discovery, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7FZ, U.K."},{"name":"3Chinese Academy for Medical Sciences Oxford Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,5,8]]},"reference":[{"key":"2024062609202262200_BST-2023-0562CC1","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1146\/annurev.biochem.67.1.425","article-title":"The ubiquitin system","volume":"67","year":"1998","journal-title":"Annu. 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