{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T16:15:09Z","timestamp":1784304909421,"version":"3.55.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>JmjC-domain-containing oxygenases are conserved epigenetic regulators whose dysfunction is closely associated with various human diseases. JMJD5, a key member of the JmjC-Domain-Only subfamily, has multiple enzymatic activities and modulates various vital physiological and pathological processes via catalytic and non-catalytic pathways. JMJD5 also displays striking tissue-specific duality in cancer: it is frequently overexpressed and acts as an oncogene in breast, prostate, and oral squamous cell carcinomas, yet is downregulated and functions as a tumor suppressor in lung, hepatocellular, and pancreatic cancers. This functional heterogeneity is closely linked to its interacting protein networks and the tumor microenvironment. Pan-cancer analyses further reveal that JMJD5 expression correlates with patient prognosis and disease progression in multiple malignancies, highlighting its potential as a prognostic biomarker. This review systematically integrates current knowledge on JMJD5 structure, enzymatic activities, physiological functions, and cancer-associated mechanisms, identifies critical research gaps, and discusses future directions for translating JMJD5 into clinical applications.<\/jats:p>","DOI":"10.3389\/fcell.2026.1818070","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:42:40Z","timestamp":1779169360000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["JMJD5: a multifunctional regulator in development, homeostasis, and cancer"],"prefix":"10.3389","volume":"14","author":[{"given":"Jing","family":"He","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haohao","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaqiong","family":"Hu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiling","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Gannan Medical University","place":["Ganzhou, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1080\/17501911.2024.2374702","article-title":"Deciphering KDM8 dysregulation and CpG methylation in hepatocellular carcinoma using multi-omics and machine learning","volume":"16","author":"Ahmed","year":"2024","journal-title":"Epigenomics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"138","DOI":"10.2533\/chimia.2026.138","article-title":"JmjC histone demethylases: beyond histone lysine demethylation","volume":"80","author":"Bonnici","year":"2026","journal-title":"Chim. 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