We recently reported that the SPOP E3 ligase and OTUD7A deubiquitinase govern EWS::FLI1 protein abundance through a ubiquitin-dependent protein stability control mechanism and demonstrated the activity of first-generation OTUD7A inhibitors in decreasing EWS::FLI1 protein levels and suppressing Ewing sarcoma growth in vitro and in animals16. The gene discussed is FLI1; the disease is Ewing sarcoma.