Lactylation as a metabolic-epigenetic nexus in epilepsy: Mechanisms and therapeutic implications

Lactylation is a novel post-translational modification (PTM) mediated by lactate, which dynamically regulates protein functions and gene expression by covalently attaching lactate groups to lysine residues. Recent studies have shown that abnormal lactate metabolism not only contributes to the pathogenesis of epilepsy through microenvironment acidification but also influences neuroinflammation, energy metabolism imbalance, neurotransmitter dysregulation, synaptic plasticity, and epigenetic regulation via lactylation. This positions lactylation as a critical metabolic-epigenetic intersection in the pathological mechanisms of epilepsy. This review systematically summarizes the molecular mechanisms of lactylation and its potential roles in epilepsy, while exploring intervention strategies targeting lactylation to provide new perspectives for epilepsy treatment.