SF3B1 is a core component of the U2 small nuclear ribonucleoprotein (snRNP) complex within the spliceosome, where it plays a critical role in pre-mRNA splicing by mediating recognition of the intron branch point sequence 1. The protein functions in both major U2-type and minor U12-type spliceosomes, facilitating the removal of introns from pre-mRNA transcripts. Mechanistically, SF3B1 participates in early spliceosome assembly and promotes selection of the branch-site adenosine required for splicing catalysis 1. Cancer-associated SF3B1 mutations, particularly hotspot mutations, cause aberrant 3' splice site selection by utilizing alternative branch point sequences, leading to cryptic splicing events 1. These mutations also impair RNA polymerase II elongation and reduce chr2 accessibility at gene promoters 2. Clinically, SF3B1 mutations are highly significant in hematological malignancies, occurring in approximately 80% of patients with myelodysplastic syndrome with ring sideroblasts (MDS-RS) 3. SF3B1-mutant MDS represents a distinct disease entity characterized by ring sideroblasts, ineffective erythropoiesis, and relatively favorable prognosis 4. The mutations serve as biomarkers for patient stratification and therapeutic decision-making, with SF3B1-mutant patients showing potential responsiveness to targeted therapies like luspatercept 43.