The majority of kidney cancers are clear cell renal cell carcinomas (ccRCC).2, 4 Recent exome sequencing of ccRCC tumors has identified almost universal mutation of the von-Hippel Lindau (VHL) tumor-suppressive gene.7, 8, 9, 10, 11 pVHL is a component of the E3 ubiquitin ligase complex, and regulates stability of the transcription factors (TFs), HIF1α and HIF2α.12 In cells with wild-type pVHL, HIF1α and HIF2α proteins are targeted for proteasome degradation under normoxic conditions, but stabilized when cells become hypoxic (HX). The gene discussed is VHL; the disease is nonpapillary renal cell carcinoma.