PRPF39 is a pre-mRNA splicing factor that functions as a homodimer to recruit U1 snRNP to weak 5' splice sites 1. Structurally, human PRPF39 forms a homodimer that interacts with the U1C CTD, functionally substituting for the yeast Prp39/Prp42 heterodimer despite increased splicing complexity in metazoans 23. The protein preferentially binds GC-rich RNA sequences and works alongside auxiliary factors including TIA1 and LUC7L isoforms to facilitate alternative splicing 1. Clinically, PRPF39 shows multiple disease relevance connections. PRPF39 expression variants affect cellular sensitivity to cisplatin chemotherapy; knockdown increases cisplatin resistance through altered expression of downstream signaling genes like MAP3K4 and TFPD2 4. Conversely, elevated circ-G004213 promotes cisplatin sensitivity in liver cancer via the miR-513b-5p/PRPF39 regulatory axis 5. Additionally, PRPF39 is overexpressed in certain cancers and serves as a DCAF15-dependent substrate for the anticancer drug E7070, suggesting therapeutic potential through targeted protein degradation 6. PRPF39 expression is regulated by NMD-inducing alternative splicing, indicating adaptive roles in cell-type-specific splicing efficiency 3.