At a genetic level, biallelic inactivation of VHL occurs in the majority of CCRCC, and also underlies the tumours that develop in families with von Hippel–Lindau disease caused by a germline mutation in VHL. Re-expression of VHL efficiently suppresses tumour growth of CCRCC in xenograft assays, establishing that VHL acts as a gatekeeper tumour suppressor gene in the renal epithelium (Iliopoulos et al, 1995). Here, VHL is linked to von Hippel-Lindau disease.