Palmitoyltransferase ZDHHC18 (ZDHHC18)

Palmitoyltransferase ZDHHC18 (ZDHHC18) is an enzyme of the zinc finger DHHC domain-containing family that catalyzes the S-palmitoylation of specific cysteine residues on a variety of protein substrates, including cGAS, HRAS and LCK, through the addition of palmitate lipid moieties[3][5]. ZDHHC18 plays a critical role in post-translational modification, modulating protein function, subcellular localization, and stability. Functionally, ZDHHC18 has been shown to negatively regulate the cGAS-STING pathway by palmitoylating and thus inactivating cGAS, thereby dampening innate immune responses against cytosolic DNA and preventing excessive activation of type I interferon signaling[1][3]. The enzyme is localized to the cytosol and is active in the Golgi apparatus[3]. ZDHHC18 is associated with several disease processes, acting as a negative regulator in antiviral responses, a potential biomarker and therapeutic target in lung adenocarcinoma, and playing a crucial role in renal fibrosis. Genetic studies also link it to neurodevelopmental disease (cerebral palsy). Therapeutic targeting of ZDHHC18, especially for fibrosis and cancer, is under investigation, though no direct pharmacological inhibitors or clinical drugs are currently reported in the literature[2][4]. Overactivity or inhibition of ZDHHC18 may pose safety concerns due to its broad regulatory functions in immunity and cell signaling.

Other names

Palmitoyltransferase ZDHHC18DHHC-18DHHC18DHHC domain-containing cysteine-rich protein 18Zinc finger DHHC domain-containing protein 18zinc finger DHHC-type containing 18zinc finger DHHC-type palmitoyltransferase 18ZDHHC palmitoyltransferase 18DKFZp667O2416

Palmitoylation of substrate proteins, which modifies their activity or function (notably inactivating cGAS and possibly modulating GPCR signaling like beta-2 adrenergic receptor)