Mechanisms and Functional Implications of ZDHHC5 in Cellular Physiology and Disease

Post-translational lipid modification by palmitoylation is a reversible process crucial for maintaining cellular functionality. The palmitoyl acyltransferase zinc finger Asp-His-His-Cys motif-containing 5 (ZDHHC5) has garnered significant attention due to its roles in neurodegenerative diseases, oncogenesis, and cardiac function. ZDHHC5 recognizes substrates through diverse mechanisms and its activity is regulated by multiple factors. Highly expressed in the brain, liver and heart, ZDHHC5 exerts regulatory functions in various cellular processes through self-regulation and substrate palmitoylation. This review focuses on the regulatory roles of ZDHHC5 in the nervous system including circadian rhythm, tumor, lipid metabolism. Dysfunctions in ZDHHC5 are associated with several diseases, thereby highlighting its potential as a target for novel therapeutic strategies against neurological, lipid metabolic, and oncogenesis.