Using a targeted shRNA screen interrogating 21 Ewing sarcoma expressed deubiquitinating enzymes, Beat Schäfer's group identified ubiquitin-specific protease USP19 as an EWS-FLI1 regulatory enzyme, whose knockdown destabilizes EWS-FLI1 protein and may therefore serve as an attractive therapeutic target. The gene discussed is FLI1; the disease is Ewing sarcoma.