Zinc finger DHHC-type palmitoyltransferase 23 (ZDHHC23)

Zinc finger DHHC-type palmitoyltransferase 23 (ZDHHC23) is a membrane-associated enzyme that catalyzes the reversible post-translational modification known as S-palmitoylation, in which a palmitate lipid is attached to cysteine residues on substrate proteins[1][5][7]. It contains a highly conserved Asp-His-His-Cys (DHHC) motif critical for its enzymatic function, and is predicted to localize mainly to the Golgi apparatus and endoplasmic reticulum[1][4]. ZDHHC23 mediates protein localization via palmitoylation, influencing the plasma membrane residency and function of substrates such as KCNMA1, with possible roles in neuronal signaling and immune regulation[1][4][3]. Disease relevance is suggested by genetic links to ataxic cerebral palsy and functional regulation of inflammation in teleost species[1][3]. Similar to other members of the zDHHC family, therapeutic targeting faces challenges relating to redundancy, substrate overlap, and the lack of selective inhibitors; the most studied inhibitor, 2-bromopalmitate, acts non-specifically across zDHHC enzymes and produces significant off-target effects[5]. Further research is needed to establish isoform-specific disease implications, biomarkers, and safe targeted therapies for ZDHHC23.

Other names

ZDHHC23Zinc finger DHHC23PALMITOYLTRANSFERASE 23

Inhibition of S-palmitoylation activity by blocking catalytic DHHC cysteine-mediated transfer of palmitate to protein substrates. Mechanistically, zDHHC23 follows the general palmitoyltransferase catalytic cycle: auto-acylation by palmitoyl-CoA, transfer of palmitate to substrate cysteine.