RBM5 (RNA binding motif protein 5) is a nuclear RNA-binding protein that functions as a key regulator of alternative splicing and apoptosis with tumor suppressor properties. As a component of the spliceosome A complex, RBM5 binds to single-stranded RNA containing the consensus sequence 5'-AGGUAA-3' and modulates splice site pairing 1. The protein exhibits dual regulatory functions in apoptosis by controlling alternative splicing of key apoptotic genes including FAS and CASP2 2. In FAS regulation, RBM5 promotes exon 6 exclusion to produce a soluble anti-apoptotic form, while in CASP2, it promotes exon 9 exclusion to generate a catalytically active pro-apoptotic form 3. RBM5 maps to the 3p21.3 tumor suppressor locus and is frequently downregulated in various cancers including lung and prostate cancers 45. Loss of RBM5 expression correlates with reduced apoptosis and increased tumor growth, while overexpression restores mitochondrial-mediated apoptotic pathways 5. Recent studies have identified RBM5 as essential for male fertility, with pathogenic variants associated with spermatogenic failure 67. Additionally, RBM5 functions as an oncogenic regulator of HOXA9 in acute myeloid leukemia, representing a potential therapeutic target 8.