As is known to all, pVHL targets two main a-subunits of hypoxia-inducible transcription factors (HIFs), including HIF-1α and HIF-2α, unlike many vascularized solid tumors, HIF-1α has opposing effects in ccRCC compared with HIF-2α. The gene discussed is EPAS1; the disease is nonpapillary renal cell carcinoma.