Together with earlier studies showing that inhibition of cyclin D1 or CDK4/6 inhibits ccRCC in vitro and in vivo (45, 50–53), our work shows that downregulation of cyclin D1 is both necessary and sufficient for the suppression of cell-autonomous ccRCC proliferation by pVHL and by pharmacologic HIF2 inhibitors. The gene discussed is CDK4; the disease is nonpapillary renal cell carcinoma.