Palmitoylation often couples with either N-myristoylation or prenylation to regulate membrane interactions of soluble proteins. N-myristoylation or prenylation of proteins in the cell cytosol provides a degree of hydrophobicity, although single lipid modifications are only sufficient for transient membrane interaction (Shahinian and Silvius, 1995) . In contrast, two closely positioned lipid modifications promote stable membrane attachment (Shahinian and Silvius, 1995) . Thus, at the cellular level, single myristoyl or prenyl chains facilitate transient membrane association, which is sufficient to allow access to membranebound DHHC proteins; subsequent palmitoylation by DHHC proteins will then promote stable membrane binding by inhibiting membrane dissociation (kinetic trapping; Fig. 1 A) . In this way, palmitoylation is essential for stable membrane association of many proteins, including farnesylated Ras and myristoylated G subunits (Hancock et al., 1990; Linder et al., 1993; Parenti et al., 1993) . Several soluble lipidated proteins are modified exclusively by S-palmitoylation, and these proteins may use an intrinsic weak membrane affinity for transient membrane interaction before palmitoylation (Greaves et al., , 2009a .