U2SURP (U2 snRNP associated SURP domain containing) is a serine/arginine-rich spliceosomal protein that functions as a regulator of alternative splicing and gene expression. As a component of the spliceosome, U2SURP interacts with other spliceosomal factors RBM17 and CHERP to reciprocally regulate their stability and control alternative splicing of RNA-processing protein transcripts 1. U2SURP contains RNA-binding domains and localizes to the nucleus and nucleoplasm, enabling its role in pre-mRNA processing 2. In cancer contexts, U2SURP is significantly upregulated and promotes tumorigenesis across multiple cancer types. In triple-negative breast cancer, MYC-driven U2SURP regulates SAT1 alternative splicing to enhance cell proliferation and metastasis 3. In pancreatic cancer, U2SURP is recruited by lncRNA HNF1A-AS1 to promote CD44 alternative splicing, facilitating invasion and metastasis 4. U2SURP expression correlates with poor survival outcomes in melanoma, breast cancer, and esophageal carcinoma, and associates with reduced immune cell infiltration and checkpoint molecule expression [PMID:40108329; 5; 60]. Functionally, silencing U2SURP suppresses cancer cell proliferation, migration, and invasion while showing minimal effects on normal epithelial cells 3. These findings establish U2SURP as a cancer-associated splicing regulator and potential therapeutic target.