Lactylation as a metabolic epigenetic modification: Mechanistic insights and regulatory pathways from cells to organs and diseases

In recent years, lactylation, a novel post-translational modification, has demonstrated a unique role in bridging cellular metabolism and epigenetic regulation. This modification exerts a dual-edged effect in both cancer and non-cancer diseases by dynamically integrating the supply of metabolic substrates and the activity of modifying enzymes: on one hand, it promotes tissue homeostasis and repair through the activation of repair genes; on the other, it exacerbates pathological progression by driving malignant phenotypes. In the field of oncology, lactylation regulates key processes such as metabolic reprogramming, immune evasion, and therapeutic resistance, thereby shaping the heterogeneity of the tumor microenvironment. In non-cancerous diseases, including neurodegeneration and cardiovascular disorders, its aberrant activation can lead to mitochondrial dysfunction, fibrosis, and chronic inflammation. Existing studies have revealed a dynamic regulatory network formed by the cooperation of modifying and demodifying enzymes, and have identified mechanisms such as subcellular localization and RNA metabolism intervention that influence disease progression. Nevertheless, several challenges remain in the field. This article comprehensively summarizes the disease-specific regulatory mechanisms of lactylation, with the aim of providing a theoretical foundation for its targeted therapeutic application.