EPAS1 and nonpapillary renal cell carcinoma: Exogenous S1P is a ligand for five high-affinity G protein-coupled receptors (S1P1–5), with specific effects depending on the suite of S1P receptor subtypes expressed.5 Representative CAKI-1 and A498 ccRCC cells express all S1P receptors, we evaluated their involvement in both HIF-1α and HIF-2α regulation.