The fact that mutations in histone modifying and chromatin remodeler genes (such as PBRM1, BAP1, SETD2, KDM5C and KDM6A) are frequent in RCC, and that the products of these genes can regulate multiple signaling pathways (e.g., mTOR, p53 and pRB–E2F), highlight the driving roles of genomic abnormalities in RCC. The gene discussed is BAP1; the disease is renal cell carcinoma.