CELF5 (CUGBP Elav-like family member 5) is an RNA-binding protein that regulates alternative mRNA splicing in a tissue-specific and developmentally controlled manner. The protein binds to muscle-specific splicing enhancer (MSE) sites and specifically activates exon 5 inclusion in cardiac troponin T (TNNT2) during heart development [UniProt]. CELF5 functions as a splicing factor that significantly regulates alternative splicing events in various tissues, including neuronal cells where it shows enrichment in astrocyte-derived extracellular vesicles with binding sites identified through motif analysis 1. In glioblastoma, CELF5 acts as a regulatory splicing factor that significantly modulates alternative splicing of GSG1L, with both positive and negative regulatory effects on different splice variants 2. The protein shows differential expression in motor neurons, where reduced CELF5 levels are associated with selective vulnerability in both spinal muscular atrophy and amyotrophic lateral sclerosis models 3. CELF5 is also upregulated in D2R-expressing neurons following morphine self-administration, suggesting roles in addiction-related transcriptomic changes 4. Additionally, CELF5 interacts with viral proteins such as HCMV UL141, potentially affecting viral DNA replication 5, and is implicated in various neurological conditions including gliomas and developmental disorders involving chromosome 19.3 duplications 67.