PTBP2 (polypyrimidine tract binding protein 2) is a neuronal RNA-binding protein that primarily functions in alternative splicing regulation. PTBP2 binds to polypyrimidine tracts and CU microsatellites in pre-mRNA, promoting exon exclusion and repressing cryptic exons to maintain splicing fidelity 1. This splicing activity is dynamically controlled during neuronal development, where the kinase KIS phosphorylates PTBP2 to modulate its RNA-binding capability and regulate exon usage 2. PTBP2 targets include SYNGAP1, where binding promotes alternative splicing and nonsense-mediated decay 3. Beyond splicing, PTBP2 exhibits oncogenic properties in multiple cancer types. In chr1 myeloid leukemia, PTBP2 stabilizes BNIP3 mRNA, promoting autophagy and cell survival while supporting tumor formation 4. Similarly, PTBP2 is aberrantly overexpressed in hepatocellular carcinoma and gliomas, where it promotes cell proliferation and migration 56. In hepatocellular carcinoma, elevated PTBP2 expression is associated with poor survival and serves as an independent prognostic factor 6. Genetically, PTBP2 variants are associated with body weight regulation and metabolic traits. Genome-wide association studies identified PTBP2 locus variants linked to both anorexia nervosa and BMI, with sex-specific effects more pronounced in males 78. Higher PTBP2 expression correlates with increased obesity risk 8.