Metabolic Function of Lactate and the Regulation and Biological Functions of Lactylation Modification

Lactate has long been regarded as a metabolic end product of glycolysis. However, recent studies have revealed its multiple functions in energy supply, signal transduction, and epigenetic regulation. This article systematically reviews the production, transport, and metabolic mechanisms of lactate, with an emphasis on its biological roles in immune regulation, inflammation control, intestinal homeostasis maintenance, and tumor microenvironment remodeling. In addition, it provides an in-depth discussion of the "writers-erasers-readers" regulatory network of lactylation. Lactylation is a lactate-driven post-translational modification that occurs on both histone and non-histone proteins. Histone lactylation primarily regulates gene transcription by altering chromatin conformation and plays key roles in macrophage polarization, inflammation resolution, and tumor progression. Non-histone lactylation extensively modifies various proteins, including metabolic enzymes and transcription factors, and participates in signal transduction, immune escape, and DNA repair. The two types of lactylation exhibit significant differences in modification sites, reaction mechanisms, and functional effects, together forming an important bridge between metabolism and epigenetic regulation. Current studies suggest that targeting lactate metabolism or lactylation-related regulatory pathways holds therapeutic potential in tumors, inflammatory diseases, and metabolic disorders. Future efforts are needed to further elucidate the dynamic regulatory networks of lactylation under pathological conditions and to facilitate its clinical translation.