Indeed, an improved understanding of the VHL gene and its downstream gene products has informed the successful development of numerous anti-cancer agents for sporadic clear cell RCC and ultimately culminated in regulatory approval by the United States Food and Drug Administration (US FDA) of the first systemic agent for patients with VHL disease-associated RCC, pNETs, or CNS hemangioblastomas [16]. The gene discussed is VHL; the disease is von Hippel-Lindau disease.