A recent study published in Nature by Radko-Juettner and colleagues reports an unexpected mutant-specific synthetic lethality in which the E3 protein ubiquitin ligase DCAF5 specifically degrades mutant but not wild-type SWI/SNF chromatin remodeling complexes.1 DCAF5 contains a likely druggable WDR domain, providing a new avenue for the development of novel therapeutics for aggressive cancers with SMARCB1 loss of function mutations. Here, DCAF5 is linked to cancer.