SF3B4 is a core subunit of the U2-type spliceosome that functions as a component of the 17S U2 SnRNP complex, directly participating in early spliceosome assembly and pre-mRNA intron removal 1. Within the SF3B subcomplex, SF3B4 is essential for 'A' complex assembly by promoting recognition of the intron branch site and selection of the branch-point adenosine, the nucleophile for the first splicing step 2. SF3B4 also participates in minor spliceosome function for U12-type intron splicing 3. Beyond its canonical splicing role, SF3B4 exhibits versatile functions in transcription, translation, and cell signaling 4. Recent studies reveal SF3B4's involvement in post-transcriptional mRNA regulation; it recruits nonsense-mediated decay (NMD) factors including UPF1, MAGOH, and RNPS1 to modulate p21 mRNA stability and cancer cell senescence 5. SF3B4 also regulates exon inclusion through interactions with HNRNPC and controls alternative splicing of chr1 remodelers affecting Hox expression 6. Clinically, SF3B4 mutations cause Nager syndrome, an acrofacial dysostosis characterized by vertebral abnormalities 6. SF3B4 is significantly upregulated in multiple cancers including hepatocellular carcinoma, triple-negative breast cancer, and promotes tumor cell survival and progression 78. SF3B4 overexpression facilitates cancer cell proliferation and metastasis through multiple pathways including FADS1-regulated ferroptosis resistance and exosomal miRNA packaging 9.