{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:35:54Z","timestamp":1790019354049,"version":"4.0.1"},"reference-count":160,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM153379"],"award-info":[{"award-number":["GM153379"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"award":["GM153379"],"award-info":[{"award-number":["GM153379"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Store-operated calcium entry (SOCE), mediated by the endoplasmic reticulum (ER) Ca2+ sensors stromal interaction molecule (STIM) proteins and the plasma membrane (PM) Orai channels, is essential for calcium signaling and a wide range of physiological processes. Precise regulation of SOCE is critical for maintaining tissue homeostasis, whereas its dysregulation contributes to diverse pathological conditions, particularly organ fibrosis. In this review, we outline the molecular basis of SOCE and discuss how its dysregulation is implicated in human disease. We further emphasize the pivotal role of SOCE in driving fibrotic progression across major organ systems. Finally, we summarize current therapeutic strategies targeting SOCE and highlight their potential for the treatment of fibrosis.<\/jats:p>","DOI":"10.3390\/cells15110980","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T13:28:21Z","timestamp":1779802101000},"page":"980","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["STIM\/Orai-Mediated Store-Operated Ca2+ Entry in the Pathogenesis of Fibrosis: Mechanisms and Therapeutic Opportunities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8054-1987","authenticated-orcid":false,"given":"Yang","family":"Yi","sequence":"first","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Nasim","family":"Uddin","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keira","family":"Killeen","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald L.","family":"Gill","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3503-0296","authenticated-orcid":false,"given":"Yandong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Cell and Biological Systems, Penn State College of Medicine, Hershey, PA 17033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1016\/j.cell.2007.11.028","article-title":"Calcium signaling","volume":"131","author":"Clapham","year":"2007","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e2424694122","DOI":"10.1073\/pnas.2424694122","article-title":"Deciphering Ca2+ permeation and valence selectivity in CaV1: Molecular dynamics simulations reveal the three-ion knock-on mechanism","volume":"122","author":"Xue","year":"2025","journal-title":"Proc. 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