S1P, one of the sphingolipid metabolites generated from ceramide by Sphk1 and Sphk2 (29), has been implicated in inflammation, neural communication, cancer, and metabolic diseases (e.g., diabetes, nonalcoholic fatty liver disease [NAFLD]) as well as organ IRI (18, 30). The gene discussed is SPHK2; the disease is diabetes mellitus.