VHL and von Hippel-Lindau disease: In the same year, it became clear that VHL inactivation is associated with abrogation of the primary cilium in renal cysts of patients with VHL disease and in VHL-defective cell lines [76] (Figure 3), and this role of VHL for ciliogenesis is independent of hypoxia-induced factor (HIF)-α abundance, suggesting two distinct functions of VHL both necessary in RCC carcinogenesis [77].