Although the absence of functional VHL protein (pVHL) and the resulting accumulation of HIF-α is crucial to ccRCC pathogenesis11, 12, 13, kidney-restricted ablation of Vhl in transgenic mice has repeatedly been shown to be insufficient to induce renal tumorigenesis14, 15, 16, 17. Here, VHL is linked to nonpapillary renal cell carcinoma.