ESRP1 is an epithelial-specific mRNA splicing regulator that controls the formation of cell-type-specific isoforms by binding GU-rich sequence motifs in target pre-mRNAs 1. It regulates splicing of multiple transcripts including FGFR2-IIIb, CD44, and CTNND1, which undergo isoform switching during epithelial-to-mesenchymal transition (EMT) 2. During placentation, ESRP1 expression suppresses trophoblast migration and invasion; ESRP1 knockdown increases cell migration associated with increased mesenchymal marker expression 3. ESRP1 dysfunction causes orofacial cleft (OFC) pathogenesis in zebrafish, mice, and humans through disrupted palatogenesis, with genome-wide association studies identifying ESRP1 variants independently associated with cleft palate and cleft lip with/without palate 42. Beyond craniofacial development, ESRP1 suppresses diffuse-type gastric cancer progression by promoting ferroptosis through DHCR7 upregulation 5, and generates tumor-suppressive circular RNAs in hepatocellular carcinoma through ESRP1-mediated circPTPN12 biogenesis, which inhibits NF-κB signaling 6. In pituitary neuroendocrine tumors, altered ESRP1 expression drives splicing abnormalities associated with worse clinical outcomes 7. High ESRP1 expression in early-onset prostate cancer predicts aggressive disease 8.