{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:11:48Z","timestamp":1790514708080,"version":"4.1.0"},"reference-count":184,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T00:00:00Z","timestamp":1633996800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Intracellular Ca2+ ions represent a signaling mediator that plays a critical role in regulating different muscular cellular processes. Ca2+ homeostasis preservation is essential for maintaining skeletal muscle structure and function. Store-operated Ca2+ entry (SOCE), a Ca2+-entry process activated by depletion of intracellular stores contributing to the regulation of various function in many cell types, is pivotal to ensure a proper Ca2+ homeostasis in muscle fibers. It is coordinated by STIM1, the main Ca2+ sensor located in the sarcoplasmic reticulum, and ORAI1 protein, a Ca2+-permeable channel located on transverse tubules. It is commonly accepted that Ca2+ entry via SOCE has the crucial role in short- and long-term muscle function, regulating and adapting many cellular processes including muscle contractility, postnatal development, myofiber phenotype and plasticity. Lack or mutations of STIM1 and\/or Orai1 and the consequent SOCE alteration have been associated with serious consequences for muscle function. Importantly, evidence suggests that SOCE alteration can trigger a change of intracellular Ca2+ signaling in skeletal muscle, participating in the pathogenesis of different progressive muscle diseases such as tubular aggregate myopathy, muscular dystrophy, cachexia, and sarcopenia. This review provides a brief overview of the molecular mechanisms underlying STIM1\/Orai1-dependent SOCE in skeletal muscle, focusing on how SOCE alteration could contribute to skeletal muscle wasting disorders and on how SOCE components could represent pharmacological targets with high therapeutic potential.<\/jats:p>","DOI":"10.3390\/cells10102722","type":"journal-article","created":{"date-parts":[[2021,10,12]],"date-time":"2021-10-12T08:09:32Z","timestamp":1634026172000},"page":"2722","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Alteration of STIM1\/Orai1-Mediated SOCE in Skeletal Muscle: Impact in Genetic Muscle Diseases and Beyond"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5125","authenticated-orcid":false,"given":"Elena","family":"Conte","sequence":"first","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9140-5350","authenticated-orcid":false,"given":"Paola","family":"Imbrici","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Mantuano","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Antonietta","family":"Coppola","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia Maria","family":"Camerino","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-7341","authenticated-orcid":false,"given":"Annamaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Liantonio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.3390\/ijms16011066","article-title":"Ca2+ dependent regulations and signaling in skeletal muscle: From electro-mechanical coupling","volume":"16","author":"Gehlert","year":"2015","journal-title":"Int. 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