Abstract: Sepsis, a life-threatening inflammatory syndrome, involves immune dysfunction, vascular homeostasis imbalance, and metabolic reprogramming. Abnormal lactate accumulation is a hallmark metabolic feature. Emerging evidence demonstrates that lactate-mediated protein lactylation contributes to sepsis progression by regulating immune cell activation, inflammatory factor expression, metabolic pathways, and cell death. Specifically, lactylation modulates the release of inflammatory factors and immune cell activity, mediates metabolic state remodeling, and influences vascular endothelial function and programmed cell death, thereby playing a critical regulatory role in sepsis pathophysiology. Although current studies link lactylation to sepsis-related inflammation, metabolic disturbances, and organ dysfunction, its integrated regulatory framework during sepsis progression remains incompletely defined. Furthermore, the theoretical basis for targeting lactylation therapeutically requires further clarification. This review systematically summarizes the regulatory functions and molecular mechanisms of lactylation in sepsis, focusing on inflammation and immune responses, metabolic reprogramming, vascular homeostasis, and programmed cell death. Our aim is to indicate subsequent mechanistic investigations and the development of targeted therapeutic interventions.

Key words: sepsis, lactylation, metabolic reprogramming, epigenetic regulation, immune modulation