The fusion protein, EWS/FLI1, binds the genome through the C-terminal DNA binding domain of FLI1, while the N-terminal EWS portion functions as a strong transactivation domain (TAD) (5). Because of the outstanding recurrence of EWS/FLI1 in Ewing sarcoma, most of our understanding of EWS function comes from the fusion context. The gene discussed is EWSR1; the disease is Ewing sarcoma.