Palmitoyltransferase ZDHHC4 (ZDHHC4)

Palmitoyltransferase ZDHHC4 (ZDHHC4) is an enzyme that catalyzes the S-palmitoylation of protein substrates, a reversible lipid modification important for membrane association, stability, and function of diverse proteins[2][3][7][8]. ZDHHC4 targets include the D(2) dopamine receptor (DRD2), glycogen synthase kinase 3 beta (GSK3B), mitochondrial antiviral-signaling protein (MAVS), and the nociceptive ion channel TRPV1[1][3][7]. It is primarily localized to the Golgi apparatus and endoplasmic reticulum[2][5]. ZDHHC4-mediated palmitoylation of TRPV1 in dorsal root ganglion (DRG) neurons promotes TRPV1 degradation and reduces nociceptive signaling during inflammatory pain, indicating a role in pain resolution through negative regulation of ion channel activity[1]. Additionally, by palmitoylating GSK3B, ZDHHC4 prevents its phosphorylation by AKT1, leading to activation of the STAT3 pathway, and palmitoylation of MAVS stabilizes and activates innate antiviral signaling[3][7]. ZDHHC4 dysfunction or altered expression has been linked to neurological conditions (paralytic lagophthalmos), cancer, infectious disease response, and neuropathic pain, underlining its therapeutic potential as an enzyme modulator or biomarker[3][8]. No drugs are currently known to directly target ZDHHC4, and no established biomarkers for patient selection or efficacy monitoring have been reported for this enzyme.

Other names

ZNF374DC1DHHC-4FLJ10479zinc finger DHHC domain-containing protein 4zinc finger protein 374zinc finger DHHC-type containing 4probable palmitoyltransferase ZDHHC4

Inhibition or modulation of enzyme (palmitoyltransferase) activity