Investigation of lipid raft biology was enhanced by the discovery of SM-specific probes, e.g., lysenin, which serve as powerful tools to study the organization and biological function of this lipid in biological membranes (Hullin-Matsuda and Kobayashi, 2007; Shogomori and Kobayashi, 2008) . These studies have demonstrated functional and structural diversity of lipid rafts and characterized in the plasma membrane of Jurkat T cells the SM-rich domains which had spatial and functional specificity compared to the GM1-rich domains (Kiyokawa et al., 2005) . Formation of SM clusters in the membranes of neuronal cells was shown to depend on localization of SM synthase (SMS) isoforms in various cell compartments and that the activity of SMS is the rate-limiting step in SM cluster formation. In accordance with this it was also demonstrated that SM clusters were formed only in the vicinity of SM synthase proteins. In particular, it was also found that the SMS2 isoform is specific for the dendrites of hippocampal neurons (Kidani et al., 2012) . The pattern of individual species of sphingomeylin was also found to be different in various types of cells and even in cell compartments (e.g., in lipid rafts versus detergent-soluble fractions) which testifies to the role of these lipids in determining cell-specific membrane properties (Valsecchi et al., 2007) .