Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5)

Zinc finger DHHC-type palmitoyltransferase 5 (ZDHHC5) is a membrane-associated enzyme that catalyzes protein S-palmitoylation, a reversible lipid modification essential for subcellular trafficking, localization, and function of diverse substrate proteins[4][6]. ZDHHC5 is distinguished by a DHHC (Asp-His-His-Cys) motif within its catalytic domain and several zinc finger structural domains, and it localizes primarily to the plasma membrane and intracellular membranes. It forms complexes with accessory proteins like GOLGA7, which regulate its stability and substrate specificity[1][4]. ZDHHC5 is involved in the palmitoylation of substrates such as the sodium-calcium exchanger (NCX1), phospholemman (PLM), and somatostatin receptor 5, influencing pathways including cardiac excitation-contraction coupling, tumor cell proliferation, synaptic plasticity, and immune responses[2][3][7]. Dysregulation of ZDHHC5 is implicated in cancer progression, cardiac hypertrophy and failure, and potentially neurological disorders, making it a therapeutic target of growing interest in both oncology and cardiology[2][3][7].

Other names

Palmitoyltransferase ZDHHC5KIAA1748ZNF375DHHC5DHHC-5Zinc finger protein 375

Inhibition of protein S-palmitoylation by blocking ZDHHC-CRD active site (e.g., Lomitapide, 2-bromopalmitate); Promotion of non-apoptotic cell death in cancer through ZDHHC5-GOLGA7 complex modulation (e.g., CIL56)