SRSF2 (serine and arginine rich splicing factor 2) is an essential RNA splicing regulatory protein that controls pre-mRNA processing and alternative splicing patterns. SRSF2 functions as a sequence-specific RNA-binding protein that recognizes specific exonic splicing enhancer motifs to regulate splice site selection 1. The protein plays a crucial role in 3'-splice site recognition during pre-mRNA processing and can interact with other splicing machinery components 2. Beyond its canonical splicing function, SRSF2 serves as a reader of m5C mRNA modifications, with structural studies identifying specific residues involved in m5C recognition 3. SRSF2 mutations are highly prevalent in myelodysplastic syndromes and acute myeloid leukemia, occurring in approximately 45-85% of myeloid neoplasms with dysplastic features 2. The most common mutation, SRSF2P95H, alters the protein's RNA-binding specificity rather than causing loss of function, leading to recurrent mis-splicing of key hematopoietic regulators including EZH2 1. This mutation impairs the protein's ability to read m5C-marked mRNAs and reduces binding to leukemia-related transcripts 3. SRSF2 mutations contribute to clonal hematopoiesis of indeterminate potential (CHIP) and create actionable neoantigens through stereotyped mis-splicing events that can be targeted by engineered T cells 45.