ZDHHC8

ZDHHC8 is a human gene that encodes a member of the ZDHHC family of zinc finger DHHC-type palmitoyltransferases. Enzymes in this family catalyze S-palmitoylation, a reversible lipid modification that attaches palmitate to cysteine residues on substrate proteins, influencing their membrane association, trafficking, stability, and interactions.

The ZDHHC8 protein contains the conserved DHHC catalytic motif and is predicted to be a transmembrane protein localized to intracellular membranes such as the Golgi apparatus and endoplasmic reticulum. As with other ZDHHC family members, its activity depends on the DHHC domain, which coordinates the transfer of palmitoyl groups to target proteins.

Expression studies show that ZDHHC8 is enriched in brain tissue, with detectable levels in regions including the cortex and hippocampus. This pattern supports a role in neuronal development and synaptic function, where palmitoylation regulates the localization and function of various synaptic and signaling proteins.

Genetic context: ZDHHC8 is located on chromosome 22q11.2, a region associated with 22q11.2 deletion syndrome. Because this region is commonly deleted in affected individuals, ZDHHC8 has been investigated as a potential contributor to the neuropsychiatric features observed in the syndrome, including associations with schizophrenia in some studies. However, the extent of ZDHHC8’s contribution remains uncertain, and findings across genetic studies have been mixed.

Functional studies in model systems have examined the consequences of altered ZDHHC8 expression on neuronal structure and synaptic signaling, with some reports describing changes in dendritic spines and synaptic function. Results across models are not entirely consistent, reflecting ongoing research into the gene’s substrates and physiological roles.

Overall, ZDHHC8 is a brain-expressed palmitoyltransferase of the ZDHHC family, with investigated but not yet definitive links to neuropsychiatric phenotypes. Further research aims to clarify its substrates, regulation, and contribution to disease.