{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:13:21Z","timestamp":1788509601868,"version":"build-2803163510"},"reference-count":70,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ubiquitin C\u2010terminal hydrolase L1 (UCHL1) is a highly conserved deubiquitinating enzyme that has transitioned from being viewed as a \u201cbrain\u2010specific\u201d protein to a global regulator of cellular proteostasis and signal transduction. As a key component of the ubiquitin\u2010proteasome system (UPS), UCHL1 maintains the intracellular free ubiquitin pool through its C\u2010terminal hydrolase activity, while also exhibiting atypical ligase\u2010like functions and acting as a molecular scaffold for signaling complexes. Beyond its classical role in neurons, increasing evidence suggests that UCHL1 participates in diverse pathological conditions including neurodegeneration, cancer, cardiovascular and metabolic diseases, as well as musculoskeletal disorders. Through regulation of protein turnover, oxidative stress, inflammatory signaling, and cell survival, UCHL1 emerges as a context\u2010dependent regulator with dual protective and pathogenic roles. This review explores the sophisticated multi\u2010level regulation of UCHL1, ranging from transcriptional control to epigenetic silencing and posttranslational modifications, summarizes the recent research progress of UCHL1 in various systems, and elaborates on its mechanism of action in various conditions, including neurological and musculoskeletal disorders.<\/jats:p>","DOI":"10.1111\/imcb.70151","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T07:49:05Z","timestamp":1785829745000},"page":"783-793","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Emerging Role of UCHL1 in Neurological and Musculoskeletal Diseases"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5154-6368","authenticated-orcid":false,"given":"Ru","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Medicine Royal Melbourne Hospital, The University of 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