We believe that the ability to regulate sphingomyelin (SM) biosynthesis could become a promising treatment for atherosclerosis.SM is one of the major lipid components in plasma and on cell membrane.We have found that plasma SM level is an independent risk factor for coronary artery disease.Thus, SM levels have a clinically important impact on lipoprotein metabolism.We also found that reduction of plasma and liver SM, with concomitant reduction of atherosclerosis, could be achieved by pharmacological inhibition of serine palmitoyltransferase (SPT) in a mouse model.Moreover, we also found sphingomyelin synthase 2 (SMS2), the last enzyme for sphingomyelin biosynthesis, deficiency in macrophages decreases SM levels on plasma membrane and thus decreases atherosclerosis in a mouse model.These observations emphasize the need for a better understanding of SM biosynthesis and atherosclerosis.