Phosphorylation also appears to regulate palmitoylation of the cyclic nucleotide phosphodiesterase (PDE) isoform PDE10A2 (Charych et al., 2010) . The N terminus of PDE10A2 contains a palmitoylated cysteine residue (Cys11) that is essential for membrane anchoring and efficient dendritic transport in striatal neurons. Palmitoylation was perturbed when phosphomimetic mutations were introduced into a downstream PKA phosphorylation site . Does phosphorylation at Thr-16 actively promote depalmitoylation of Cys-11, or does it block palmitoylation of this cysteine? In fact, PKA activation markedly enhanced PDE10A2 phosphorylation but had no acute effect on membrane expression levels. This observation suggests that phosphorylation does not promote depalmitoylation and membrane release of PDE10A2 but, instead, likely inhibits membrane binding by blocking palmitoylation. This phosphoregulation of palmitoylation might be relevant to many palmitoylated peripheral proteins and could represent a mechanism to promote a shift toward the depalmitoylated state of a protein in the absence of active (thioesterase driven) depalmitoylation. Negatively charged phosphate groups are likely to inhibit palmitoylation of neighboring cysteines by interfering with membrane interactions before palmitoylation (Fig. 3) .