Earlier reports from our laboratory have demonstrated that ASM plays an essential role in forming ceramide-enriched MR clusters in ECs, in which NOX subunits are aggregated and activated leading to redox signaling and consequent endothelial NLRP3 inflammasome activation and arterial neointima formation during hypercholesterolemia (18, 24). This evidence concerns the gene SMPD1 and familial hypercholesterolemia.