Histone lactylation: Unveiling a novel pathway for the impact of lactate on physiological and pathological processes...

Histone lactylation, a novel epigenetic modification, has emerged as a critical mediator of various physiological and pathological processes. The present review elucidates the molecular mechanisms of lysine lactylation (Kla) and its influence on gene expression modulation. In addition, previous findings regarding the mechanisms of Kla and its impact on metabolic regulation, inflammation and tumorigenesis are summarized. Histone lactylation influences macrophage polarization, promotes tumor immune evasion, and affects osteoblast differentiation and embryonic development. While promising as a therapeutic target, research progress is currently hindered by methodological limitations in terms of lactylation quantification and manipulation. The current review not only summarizes fundamental insights into Kla‑mediated disease pathogenesis but also critically addresses existing knowledge gaps. By highlighting the dynamic interplay between lactylation and metabolic regulation, novel perspectives are provided on the biological importance of this posttranslational modification. Ultimately, the aim of this review is to identify innovative approaches for targeting lactylation‑mediated pathways in disease treatment.