Unlike the catalysts of N-myristoylation and prenylation reactions, the enzymes that mediate palmitoylation are polytopic membrane proteins (Fukata et al., 2004; Mitchell et al., 2006) , implying that cellular palmitoylation reactions occur at the cytosol-membrane interface. There are 23 putative S-palmitoyl transferases in mammals, characterized by the presence of a DHHC (aspartate-histidine-histidine-cysteine) motif within an 50 amino acid cysteine-rich domain. The large number of these DHHC proteins coupled with their localization to distinct membrane compartments (Ohno et al., 2006) implies that the cellular palmitoylation machinery is a highly regulated and coordinated system.