Some studies have given rise to a model of VHL-associated kidney disease progression in which loss of the cilia maintenance function of pVHL predisposes patients to develop cysts owing to secondary mutations that result in inactivation of GSK3β, and additional mutations in cystic cells and loss of the HIFα degradation function of pVHL are probably required for further progression from cystic precursor to ccRCC, and which suggests a cyst-dependent progression pathway of ccRCC in VHL disease [17–20]. Here, VHL is linked to kidney disorder.