Remarkably, in endometrial cancer, some SPOP SRD mutations, such as R121Q, lead to an enhanced association between SPOP and BET-family members, which results in increased ubiquitylation, decreased BET protein levels and enhanced sensitivity to BETi.106 This underscores the importance of understanding the nature of mutations in their appropriate biological context. The gene discussed is SPOP; the disease is endometrial cancer.