Pulmonary fibrosis (PF) is a progressive and irreversible interstitial lung disease that is characterized by destruction of alveolar architecture, excessive proliferation of fibroblasts, and aberrant deposition of extracellular matrix (ECM) but the precise pathogenesis has yet to be fully elucidated. Although traditionally regarded as the terminal metabolite of glycolysis, lactate has been reappreciated, especially following the rise of metabolic reprogramming concepts after the Warburg effect, as an important signaling molecule capable of actively regulating diverse cellular functions. Among these cellular functions, the lactate-induced post-translational modification (PTM), known as lactylation, offers a new perspective for understanding the broad biological actions of lactate beyond metabolism. Notably, the pathologic microenvironment of PF is characterized by widespread metabolic reprogramming and lactate accumulation, suggesting that lactate and lactate-mediated lactylation may serve key roles in disease progression by regulating pro-fibrotic gene expression and influencing fibroblast activation and differentiation. Therefore, this review focuses on how lactylation functions as a bridge linking metabolic reprogramming to fibrotic phenotypes in PF and the translational potential as a novel therapeutic target is discussed.
Wang et al. (2026) studied this question.