Landmark studies in yeast highlighted the DHHC protein family as the catalysts of intracellular membrane fusion reactions and provided an essential spark to the palmitoylation field. This, together with the continuing development of new methodologies and reagents, has served as a platform for rapid expansion in our understanding of the mechanisms, spatiotemporal dynamics, and outcomes of protein palmitoylation. Techniques such as acyl-biotin exchange and click chemistry have offered highly sensitive alternatives to radiolabeling for the study of cellular palmitoylation (Drisdel and Green, 2004; Martin and Cravatt, 2009; Yap et al., 2010) . These approaches also permit the palmitoylation status of proteins to be studied in situ without cell labeling (acyl-biotin exchange) or the analysis of spatial patterns of palmitoylated proteins by fluorescence imaging (Hannoush and Arenas-Ramirez, 2009 ). Furthermore, both techniques have facilitated analysis of the cellular palmitoylome in both yeast and mammalian cells (Roth et al., 2006; Kang et al., 2008; Martin and Cravatt, 2009 ). The recent development of Apt1 inhibitors is an important step toward further delineating the function of this protein and developing an enhanced understanding of cellular depalmitoylation dynamics (Dekker et al., 2010) . It is expected that further technological developments will maintain the rapid pace of palmitoylation research. In particular, the development of more specific and selective inhibitors against the DHHC protein family (Resh, 2006b) will be a key to delineating the individual functions of these proteins and their contribution to the spatiotemporal dynamics of cellular palmitoylation reactions. site that regulate plasma membrane binding of the cytosolic C terminus (Tian et al., 2008) . Introduction of a phosphomimetic mutation at the PKA phosphorylation site or activation of cellular PKA perturbed palmitoylation-dependent membrane association of the C-terminal tail of STREX. Importantly, the full-length channel lacking the palmitoylated cysteines in the STREX domain was no longer subject to PKA-mediated inhibition, implying that phospho-regulation of the STREX channel is achieved via changes in palmitoylation and membrane association of the cytoplasmic C terminus.