S-palmitoylation regulates innate immune signaling pathways: molecular mechanisms and targeted therapies

S-palmitoylation is a reversible posttranslational lipid modification that targets cysteine residues of proteins and plays critical roles in regulating the biological processes of substrate proteins. The innate immune system serves as the first line of defense against pathogenic invaders and participates in the maintenance of tissue homeostasis. Emerging studies have uncovered the functions of S-palmitoylation in modulating innate immune responses. In this review, we focus on the reversible palmitoylation of innate immune signaling proteins, with particular emphasis on its roles in the regulation of protein localization, protein stability, and protein-protein interactions. We also highlight the potential and challenge of developing therapies that target S-palmitoylation or de-palmitoylation for various diseases.