DHHC palmitoyl transferases: substrate interactions and (patho)physiology

S-palmitoylation is a reversible post-translational modification that occurs on diverse cellular proteins. Palmitoylation can affect proteins in many different ways, including regulating membrane attachment, intracellular trafficking, and membrane micro-localisation. Intracellular palmitoylation reactions are mediated by a family of recently identified aspartate–histidine–histidine–cysteine (DHHC) palmitoyl transferases. More than 20 DHHC proteins are encoded by mammalian genomes, and there is now a major effort to identify DHHC–substrate pairings and to determine how interaction specificity is encoded. Recent studies have highlighted how DHHC proteins regulate cell function and influence physiology and pathophysiology.