RBM22 is an RNA-binding protein essential for pre-mRNA splicing as a component of the activated spliceosome 1. It binds directly to the U6 snRNA internal stem-loop domain and pre-mRNA intron sequences near the 5' splice site, promoting an active conformation of the spliceosome catalytic center during splicing catalysis 2. Structurally, the intron lariat traverses through RBM22's positively charged central channel, suggesting roles in intron recruitment and release 3. Beyond splicing, RBM22 regulates RNA polymerase II transcription by coordinating the 7SK-P-TEFb complex and SPT5, controlling promoter pause release, elongation kinetics, and termination 4. RBM22 also functions as a transcriptional regulator binding cell cycle gene promoters cooperatively with chr5 remodeler SMARCA4 to enhance accessibility and drive transcription 5. Disease relevance is substantial: RBM22 dysregulation correlates with glioblastoma aggressiveness and patient survival 6, and RBM22 depletion impairs cell cycle progression in myeloid cells, relevant to myelodysplastic syndromes with del(5q) 7. In colon cancer, RBM22 suppresses proliferation and induces apoptosis via c-Myc pathway modulation 8. Clinically, RBM22 restoration promotes cardiomyocyte proliferation and cardiac regeneration after injury 5, indicating therapeutic potential in cardiac repair.