The Ras cycling pathway is an example of how constitutive palmitoylation dynamics coordinate protein sorting. For some proteins, palmitoylation turnover and corresponding changes in intracellular localization can also be regulated by cell activity. Protein palmitoylation dynamics that are subject to regulation have been particularly well characterized for postsynaptic proteins; palmitoylation of the molecular scaffold PSD95 and AMPA and NMDA glutamate receptors are all regulated by synaptic activity (El-Husseini et al., 2002; Hayashi et al., 2005 Hayashi et al., , 2009 ). PSD95 is a peripheral palmitoylated protein that coordinates protein clustering at postsynaptic sites. This protein was suggested to display a decreased palmitoylation in response to glutamate receptor activation, which corresponded with a reduced synaptic clustering of both PSD95 and AMPA receptors. Palmitoylation of GluR1/GluR2 subunits of AMPA receptors and NR2A/2B subunits of NMDA receptors is also modulated by synaptic activity. The palmitoylation status of GluR1 affects association with the 4.1N protein, regulating activity-dependent receptor internalization and plasma membrane insertion dynamics (Hayashi et al., 2005; Lin et al., 2009) . Dynamic palmitoylation of NR2 subunits also modulates cell surface expression of the NMDA receptor ). Thus, neurons use dynamic palmitoylation as a response mode to couple changes in synaptic activity to changes in protein localization.