Recent advances in research on the association between lactylation and regulated cell death in sepsis

BACKGROUND: Sepsis is a life-threatening organ dysfunction mediated by host immune dysregulation, and elevated serum lactate levels are an important pathophysiological feature. Lactate is not only the terminal product of glucose metabolism but also acts as a signaling molecule that regulates gene expression and protein function through lactylation. Regulated cell death (RCD), as a targetable terminal cell fate, offers a potential direction for precision intervention in sepsis. OBJECTIVE: Although studies have indicated that lactylation can affect sepsis progression by regulating RCD, no review has systematically summarized this relationship. Therefore, this review systematically summarizes the regulatory roles of lactylation in RCD and their pathological significance in sepsis. INNOVATION: Based on the above evidence, this review proposes that "lactylation modification imbalance-aberrant activation of RCD" may be a potential driving mechanism of sepsis progression and that the lactylation/acetylation imbalance caused by glucose metabolism reprogramming is an upstream regulatory link of this axis. CONCLUSION: In summary, targeting lactylation modification to precisely modulate RCD may interrupt the pathological chain from lactate elevation to organ injury, providing new perspectives for sepsis treatment research.