RBM39 (RNA binding motif protein 39) is an essential RNA-binding protein that functions primarily as a pre-mRNA splicing factor, promoting exon inclusion through regulation of exon cassette splicing 12. The protein associates with precursor mRNA splicing factors and plays a crucial role in maintaining proper RNA splicing patterns 1. Beyond its splicing function, RBM39 serves as a metabolic regulator, binding arginine to control expression of metabolic genes in hepatocellular carcinoma, creating feedback loops that sustain oncogenic metabolism 3. RBM39 also functions as a transcriptional coactivator, interacting with proteins like JMJD6 to regulate gene expression, including DGAT1 in clear cell renal cell carcinoma 4. Clinically, RBM39 represents a significant therapeutic target across multiple cancers. The protein can be pharmacologically targeted through sulfonamide drugs like indisulam, which promote RBM39 degradation via recruitment to the DCAF15 E3 ubiquitin ligase complex 15. RBM39 dependency is particularly pronounced in acute myeloid leukemia and B-cell acute lymphoblastic leukemia, where its targeting shows promising anti-tumor activity 26. Additionally, RBM39 degradation can enhance anti-tumor immunity by generating splicing-derived neoantigens 7.