Thus far, several spliceosome components and regulatory RBPs have been identified to modulate variant splicing of two BCL2 family members, BCLx and MCL1. The splicing control of BCLx and MCL1 is central for regular apoptotic response in normal development with aberrant control of these proteins leading to tumorigenesis, cancer progression, and drug insensitivity. The gene discussed is BCL2; the disease is cancer.