KHDRBS2 is an RNA-binding protein containing a KH domain embedded within a conserved STAR domain that regulates alternative splicing and mRNA metabolism 1. The protein binds poly(A) and poly(U) homopolymers and modulates splice site selection through direct interaction with RNA sequences, exemplified by concentration-dependent exon inclusion in CD44 pre-mRNA [UniProt]. Phosphorylation by tyrosine kinases (PTK6, FYN) inhibits its RNA-binding and splicing regulatory functions, while phosphorylation by Src during mitosis may facilitate adapter protein function for tyrosine kinase signaling 1. KHDRBS2 exhibits cell-type-specific regulation of neurexin alternative splicing, working synergistically or antagonistically with SAM68 depending on target and context [UniProt]. Clinically, KHDRBS2 demonstrates disease relevance across multiple conditions: in prostate cancer, KHDRBS2 regulates androgen receptor splice variant 7 (AR-V7) expression, a critical factor in castration-resistant prostate cancer progression 2; in glioblastoma, low KHDRBS2 expression correlates with poor prognosis and reduced anti-tumor immune infiltration 3; and it serves as a diagnostic biomarker in nasopharyngeal carcinoma with high discriminatory power (AUC=0.978) 4. Additionally, KHDRBS2 shows genetic associations with Alzheimer's disease through epistatic interactions and with Barrett's esophagus/esophageal adenocarcinoma in males 56, and demonstrates signatures of positive selection in Tibetan high-altitude adaptation 7.