Sphingomyelin synthase that primarily contributes to sphingomyelin synthesis and homeostasis at the plasma membrane (PubMed:19590047, PubMed:21844222, PubMed:22580896). Catalyzes the reversible transfer of phosphocholine moiety in sphingomyelin biosynthesis: in the forward reaction transfers phosphocholine head group of phosphatidylcholine (PC) on to ceramide (CER) to form ceramide phosphocholine (sphingomyelin, SM) and diacylglycerol (DAG) as by-product, and in the reverse reaction transfers phosphocholine from SM to DAG to form PC and CER. The direction of the reaction appears to depend on the levels of CER and DAG in the plasma membrane. Does not use free phosphorylcholine or CDP-choline as donors (By similarity). Can also transfer phosphoethanolamine head group of phosphatidylethanolamine (PE) on to ceramide (CER) to form ceramide phosphoethanolamine (CPE) (By similarity). Regulates receptor-mediated signal transduction via mitogenic DAG and proapoptotic CER, as well as via SM, a structural component of membrane rafts that serve as platforms for signal transduction and protein sorting (PubMed:19590047, PubMed:21844222). To a lesser extent, plays a role in secretory transport via regulation of DAG pool at the Golgi apparatus and its downstream effects on PRKD1. Required for normal bone matrix mineralization (By similarity). a 1,2-diacyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine = a 1,2-diacyl-sn-glycerol + a sphingomyelin 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine = 1,2-dihexadecanoyl-sn-glycerol + a sphingomyelin 1-(9Z-octadecenoyl)-2-acyl-sn-3-glycerol + a sphingomyelin = a 1-(9Z-octadecenoyl)-2-acyl-sn-glycero-3-phosphocholine + an N-acylsphing-4-enine a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-sphinganine-1-phosphocholine a 1,2-diacyl-sn-glycero-3-phosphocholine + N-hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-(4R)-hydroxysphinganine-phosphocholine a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-hexadecanoylsphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-sphinganine-1-phosphoethanolamine a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + N-hexadecanoyl-(4R)-hydroxysphinganine = a 1,2-diacyl-sn-glycerol + N-hexadecanoyl-(4R)-hydroxysphinganine-1-phosphoethanolamine Sphingolipid metabolism. Primarily localized at the plasma membrane with a small fraction at the Golgi apparatus. Highest expression is detected in cortical bone, followed by vertebrae, kidney and liver. Expression levels are very low in spleen, muscle, heart, brown fat and thymus (PubMed:30779713). Expressed in macrophages. Palmitoylated on Cys-331, Cys-332, Cys-343 and Cys-348; which plays an important role in plasma membrane localization. Null mice are viable but exhibit increased cell membrane ceramide and decreased sphingomyelin levels. In both skeletal muscle and adipose tissue, there is a significant increase in glucose uptake. This leads to increased insulin sensitivity and ameliorated high-fat diet-induced obesity. There is blunted NFKB1- and MAP kinase-mediated responses to inflammatory stimuli and macrophages display increased cholesterol efflux into blood circulation. Liver SMS activity is markedly reduced (by about 80%) but only small change in macrophage SMS2 activity (16%). No change in glycosphingolipid levels in plasma. Atherosclerosis in SMS2(-/-)/LDLR(-/-) mice is significantly decreased. Belongs to the sphingomyelin synthase family.