SRSF1 (serine and arginine-rich splicing factor 1) is a multifunctional RNA-binding protein that regulates alternative splicing through interaction with spliceosomal components, binding purine-rich RNA sequences to enhance or suppress exon inclusion 1. Beyond canonical splicing regulation, SRSF1 functions as a key node integrating cellular stress responses and metabolic pathways. In endothelial cells, SRSF1 accumulates under hypoxic conditions and promotes ischemia-induced angiogenesis by modulating alternative splicing of ATF3, which subsequently suppresses the KLF2-S1PR1 inhibitory pathway 1. SRSF1 expression is regulated downstream of mTORC1 signaling through SRPK2-mediated phosphorylation, coupling transcription and splicing of lipogenic enzymes via interaction with FAM120A and SREBP1 2. Clinically, SRSF1 dysregulation drives multiple malignancies. In pancreatic cancer, elevated SRSF1 promotes pancreatitis and KRASG12D-mediated tumorigenesis by upregulating IL1R1 through alternative splicing, though negative feedback normally constrains this activity 3. In prostate cancer, FOXA1-controlled SRSF1 orchestrates alternative splicing of NMD-sensitive isoforms, including FLNA exon 30 inclusion, predicting disease recurrence 4. SRSF1 is recurrently mutated in Richter syndrome transformation from chr17 lymphocytic leukemia 5. Importantly, SRSF1 inhibition via small-molecule targeting simultaneously reprograms tumor metabolism and enhances CD8+ T cell antitumor immunity, representing a dual-action immunotherapeutic strategy 6.