In addition to specific roles of specific lipid species, the compartmentalization of lipids and associated signaling is now appreciated as an important component of signal transduction. Moreover, as the cloned nSMases have been observed in multiple organelles, it is extremely important to not only investigate the mechanisms underlying their cellular trafficking but also to consider the compartment-specific activities and functional consequences. This information will not only provide further insight into sphingolipid signaling and regulation in individual subcellular compartments but will also shed light on the physiological functions of the individual N-SMases.