Many clear cell renal cell carcinomas (ccRCC) harbour ubiquitin carboxyl-terminal hydrolase BAP1 (BAP1) and protein polybromo-1 (PBRM1) mutations. Now, data from genetically modified mouse models indicate that conditional Bap1 or Pbrm1 knockout with Von Hippel–Lindau codeletion results in ccRCC of different grades: Bap1-deficient tumours had a higher grade with greater serine/threonine-protein kinase mTOR activation, relative to Pbrm1-deficient tumours, which had a longer latency.