SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 2 (SMARCA2) selective protein degraders, such as PRT3789, offer a unique approach by exploiting synthetic lethality in SMARCA4-deficient tumors with >1000-fold selectivity for SMARCA4-mutated cancer cells compared to wild-type cells [31]. The gene discussed is SMARCA4; the disease is cancer.