Loss and impairment of VHL lead to the stabilization of hypoxia-inducible factor proteins that upregulate the expression of cellular proliferation and angiogenesis genes, such as vascular endothelial growth factor, and elevate the corresponding protein levels, and these findings directly prompt the application of tyrosine kinase inhibitors (TKIs), a revolutionary treatment for ccRCC patients 2, 3. The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.