Recently, the understanding of accumulation of HIF-2α within the cell as a result of VHL inactivation has led to the development of belzutifan, the first oral HIF-2α inhibitor approved by the FDA in 2021 for treatment of adult patients with VHL associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Here, EPAS1 is linked to renal cell carcinoma.