Zinc finger DHHC-type palmitoyltransferase 15 (ZDHHC15)

Zinc finger DHHC-type palmitoyltransferase 15 (ZDHHC15) is a protein-coding enzyme that catalyzes the addition of fatty acids (mainly palmitate, but also myristate and stearate) to substrate proteins, regulating processes such as protein trafficking and synaptic function. Containing a DHHC (Asp-His-His-Cys) palmitoyltransferase domain and a zinc finger, ZDHHC15 localizes to intracellular membranes, especially affecting endosomal and Golgi trafficking, and is highly expressed in nervous tissue where it modulates key synaptic proteins like DLG4/PSD95. Mutations or loss of ZDHHC15 are strongly linked to X-linked intellectual developmental disorder (MRX91), and roles in neurological development, glioma progression, and autism spectrum disorders have been described. Alternative splicing produces different isoforms with tissue-specific expression; substrate diversity gives rise to complex functional consequences when the enzyme is disrupted.

Other names

ZDHHC palmitoyltransferase 15DHHC-15MRX91Mental retardation, X-linked 91Acyltransferase ZDHHC15Zinc finger DHHC domain-containing protein 15Zinc finger, DHHC domain containing 15

As an enzyme, drugs targeting ZDHHC15 would most likely inhibit its palmitoyltransferase activity, blocking the transfer of fatty acids to protein substrates. Inhibition would thus alter substrate trafficking, localization, and stability, impacting synaptic function and potentially neurodevelopmental disease processes.