New insights into lactylation in respiratory diseases: progress and perspectives

Lactate is conventionally regarded as a metabolic byproduct and generated through diverse pathophysiological pathways. However, a growing body of evidence supports its regulatory roles in energy metabolism and signal transduction, boosting extensive research into lactate-mediated lactylation as a newly discovered post-translational modification (PTM). Lactylation can occur on both histone and non-histone proteins, thereby modulating gene transcription and protein function. By influencing various biological processes, lactylation has been shown to intricately participate in the onset and progression of respiratory diseases that are closely related to metabolic abnormalities and remodeling, including asthma, lung cancer, pulmonary fibrosis, silicosis, pulmonary hypertension (PH), and acute lung injury (ALI). In this review, we summarize the current progress in this field, underscoring the multifaceted regulatory and functional mechanisms underlying lactylation, the pivotal role of lactylation in different respiratory diseases, as well with its potential as a therapeutic target. This comprehensive understanding offers novel insights into the pathogenesis of respiratory diseases and opens new avenues for therapeutic approach.