The main lipid components of the cell membrane are sphingolipids, cholesterol and other phospholipids. The predominant element of the sphingolipid molecule in the cell membrane is sphingomyelin, which is composed of a hydrophilic phosphorylcholine head and a highly hydrophobic ceramide molecule. The ceramide group in sphingomyelin is composed of the amide ester of the sphingoid base D-erythro-sphingosine and a fatty acid with a chain length of C16-C26. The lateral association of sphingolipids and cholesterol is promoted by a strong interaction between the cholesterol-sterol ring structure and the ceramide molecule of sphingomyelin, which is facilitated by hydrogen bonds and hydrophobic van der Waal interactions in addition to hydrophilic interactions and therefore by cleavage from other phospholipids into distinct microdomains (Brown & London, 1998). These microdomains have been defined as rafts that serve a function in the aggregation of receptor molecules and the reorganization of intracellular signaling molecules to transmit a signal into the cell. Sphingomyelin (SM) appears to be the major sphingolipid source for bioactive ceramide in the vast majority of cells, thus underscoring the major functions of ASMs in initiating ceramide signaling (Perrotta et al., 2010). ASM was initially recognized as a cation-independent hydrolase involved in the catabolism of SM in lysosomes ( Horinouchi et al., 1995 ). There are now two types of acid sphingomylinase. The first is lysosomal acid sphingomylinase (L-ASM) which has an important role in the production of ceramide as a response of the cell to stresses such as infections, environmental insults, ligation of death receptors and exposure to chemotherapeutic drugs. Transfer of L-ASM to the lysosome is vi... middle of paper... is most evident in endothelial cells. Possibly, the absence of functional ASM inhibits ceramide production and the reorganization of membrane rafts into platforms, protecting against cell death. By introducing a partially functional SMPD1 gene into the completely knockout (ASMKO) background, a transgenic type B NPD mouse model was produced, resulting in a mouse with approximately 8% residual ASM activity in most organs (Marathe et al ., 2000). Notably, these mice never develop a neurological phenotype and live normal lives. However, around 8-10 months of age they begin to show lipid deposits in the RES organs. These interpretations provide in vivo evidence that low levels of ASM activity in the brain can prevent neurological disease in patients with ASM and have important applications for the treatment of NPD with neurological ASM deficiency (type A)..