Protein S-palmitoylation: Dynamic regulatory networks, physiological functions, and new frontiers in targeted therapy

S-palmitoylation, a key reversible lipid post-translational modification, entails the covalent conjugation of palmitic acid chains to the thiol groups of cysteine residues in proteins. This modification modulates protein localization, stability, and interactions, thereby contributing to essential physiological processes such as cellular signal transduction and immune activation. Dysregulation of S-palmitoylation is closely linked to major diseases including tumors, neurodegenerative disorders, and immune disorders, establishing it as a prominent research focus at the intersection of life sciences and medicine. This review aims to systematically synthesize advances in S-palmitoylation research, by dissecting its core regulatory mechanisms, physiological and pathological roles, technological innovations, and targeted therapeutic strategies to summarize the current status and key challenges in the field. It offers a comprehensive framework for understanding the regulatory principles and disease relevance of this modification, while providing valuable references for basic research and the development of disease-targeted therapies.