Recent advances in S-palmitoylation and its emerging roles in human diseases.

S-palmitoylation, one reversible post-translational modification (PTM) involving the binding of palmitate to proteins, influences protein stability, localization and interactions. Through S-palmitoylation, proteins can be targeted to specific cellular compartments, form functional complexes, and participate in intricate signaling cascades. Organized and reversible S-palmitoylation process achieves remarkable roles in the precise orchestration of biological activities, including cell signaling, membrane trafficking, synaptic transmission and cellular immunity. S-palmitoylation has been implicated in the pathogenesis of diverse disorders including cancers, cardiovascular diseases, metabolic diseases, immunological diseases, infection diseases, nervous system and mental diseases. Altered S-palmitoylation of proteins changes the oncogenic function, synaptic localization, enzymatic activity and signaling transduction, potentially contributing to disease progression. Understanding and targeting S-palmitoylation pathways hold promise for therapeutic interventions in associated diseases. Collectively, S-palmitoylation is a key regulatory mechanism with significant implications for disease pathogenesis. Investigating the role of S-palmitoylation provides insights into diagnostic markers and potential therapeutic targets, highlighting the importance of ongoing research in understanding the broader implications of S-palmitoylation in health and disease.