APOE and Hypercholesterolemia: Although we, too, have observed intracellular cholesterol accumulation and impaired ABCA1-mediated cholesterol efflux in S1P lyase-inhibited or -deficient macrophages, the accompanying hypercholesterolemia and acceleration of atherosclerosis are uncommon to global ABCA1 deficiency either on the ApoE−/− or LDLR−/− background [40].