This paper reviews how adding small chemical groups (like acetyl, lactyl, or palmitoyl) to proteins changes how immune cells work and can cause inflammation‑related diseases. It explains the enzymes that add or remove these groups and suggests that targeting them could become new treatments, but it doesn’t give any direct tips for using palmitoyl‑dipeptide‑6 or other supplements.

Protein acylation, a critical subset of post-translational modifications (PTMs), serves as a dynamic regulatory mechanism linking cellular metabolism, epigenetic regulation, and inflammatory responses. This review systematically elucidates the roles of protein acylation modifications-including acetylation, lactylation, succinylation, propionylation, crotonylation, malonylation, butyrylation, S-palmitoylation, and myristoylation-in the pathogenesis of inflammatory diseases. These modifications, orchestrated by acyltransferases (writers), deacylases (erasers), and recognition proteins (readers), regulate immune cell functionality and disease progression. In immune cells, specific acylation patterns govern inflammatory responses by modulating polarization, cytokine production, and signaling pathways. Furthermore, dysregulated protein acylation contributes to the pathogenesis of inflammatory diseases such as sepsis, periodontitis, inflammatory bowel disease, atherosclerosis, and rheumatoid arthritis through disrupting immune homeostasis, driving metabolic reprogramming, and impairing tissue repair. Emerging therapeutic strategies targeting acylation-related enzymes or leveraging nanoparticle-based drug delivery systems show promise in restoring balanced PTM dynamics and alleviating disease progression. By systematically mapping protein acylation networks across immune and diseased cells, this review provides insights into novel diagnostic biomarkers and therapeutic interventions for inflammatory diseases.