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). This evidence concerns the gene EPAS1 and nonpapillary renal cell carcinoma.