What is the underlying mechanistic basis for the effects of palmitoylation on protein sorting? For some soluble proteins, palmitoylation may be a passive sorting signal, acting only as an essential membrane anchor that allows other domains of the protein to regulate subsequent trafficking. However, palmitoylation also has active effects on protein sorting, achieved by partitioning of proteins into cholesterol-rich membrane subdomains or rafts (Levental et al., 2010) , changing protein orientation at the membrane and thus affecting protein-protein interactions (Hayashi et al., 2005; Lin et al., 2009) , regulating the ubiquitination status of proteins and thereby modulating ubiquitinationdependent protein sorting (Valdez-Taubas and Pelham, 2005; Linder and Deschenes, 2007; Abrami et al., 2008) , or affecting the transmembrane orientation of palmitoylated proteins in the membrane bilayer (Abrami et al., 2008) .