The role of protein palmitoylation in disease pathogenesis and therapeutic innovation

BACKGROUND: Protein palmitoylation is a significant post-translational modification that influences protein stability, localization, and signaling through the addition of palmitoyl groups to cysteine, serine/threonine, or lysine residues. It is facilitated by palmitoyltransferases (e.g. zDHHC family) and reversed by depalmitoylases such as APT1/2. Dysregulation of this modification has been associated with several diseases, including diabetes and cancer. OBJECTIVE: This review aims to evaluate the role of palmitoylation in metabolic disorders and cancer, as well as to assess recent therapeutic strategies aimed at targeting this modification. METHODS: A literature review was conducted focusing on the implications of S-palmitoylation, N-palmitoylation, and O-palmitoylation in various diseases, and the effectiveness of recent therapeutic approaches that target these pathways. CONCLUSION: Findings highlight the critical role of palmitoylation in disease mechanisms and therapeutic potentials. While promising strategies have emerged, challenges remain in developing selective inhibitors for the zDHHC enzymes. Ongoing research is necessary to further elucidate the molecular mechanisms and advance drug development tailored to manage metabolic diseases and cancer.