{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T05:05:10Z","timestamp":1784005510357,"version":"3.55.0"},"reference-count":62,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"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. Mol. Biosci."],"abstract":"<jats:p>CELF4 (CUGBP Elav-like family member 4), encoded by the human chromosome 18q12.2 locus, is an RNA-binding protein that recognizes UG-rich sequences within the 3\u2032untranslated region (3\u2032UTR) of target mRNAs to regulate splicing, stability, and local translation at the post-transcriptional level. Under physiological conditions, CELF4 exerts translational repression during synaptic development in the central nervous system (CNS), maintains excitatory homeostasis, and sets peripheral sensory thresholds; in cardiac fibroblasts, it is expressed at low levels and restricts baseline TGF-\u03b2 signaling. In pathological states, CELF4 exhibits context-dependent bidirectional modulation: in autism spectrum disorder (ASD), major depressive disorder (MDD), epilepsy, chronic pain, and endometrial cancer, its downregulation or epigenetic silencing causes translational derepression of target mRNAs; in cardiac fibrosis, TGF-\u03b21-induced upregulation suppresses FMO2 translation and activates the Smad2\/3 pathway. Additionally, pleiotropic genetic loci near CELF4 have been linked to gut-brain axis comorbidities and obesity-hypertension syndromes. Clinically, CELF4 promoter methylation testing has entered validation trials for non-invasive endometrial cancer screening, and its haploinsufficiency has been incorporated into the genetic diagnosis of 18q12.2 microdeletion syndrome; pharmacological and gene-replacement strategies targeting CELF4 remain at the preclinical proof-of-concept stage. Here, we review the molecular regulatory networks of CELF4 and its mechanisms across multisystem diseases, discuss the current status and limitations of clinical translation, and may guide future research on diagnostic biomarkers and therapeutic strategies targeting this protein.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1883784","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T04:22:02Z","timestamp":1784002922000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The RNA-binding protein CELF4: from molecular regulatory networks to clinical translation in cross-system diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Qingsong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pediatrics, West China Hospital Sichuan University Jintang Hospital. 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Jintang First People\u2019s Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Guancang Community Health Service Center","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Center, Sichuan Provincial Women\u2019s and Children\u2019s Hospital, The Affiliated Women\u2019s and Children\u2019s Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongyong","family":"Luo","sequence":"additional","affiliation":[{"name":"Pediatric Cardiology Center, Sichuan Provincial Women\u2019s and Children\u2019s Hospital, The Affiliated Women\u2019s and Children\u2019s Hospital of Chengdu Medical College","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Ultrasound, West China Hospital Sichuan University Jintang Hospital. 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