High altitude cerebral edema (HACE), a fatal terminal stage of acute mountain sickness (AMS), is triggered by rapid exposure to hypoxia at high altitudes. The pathophysiology of HACE is complex, involving multiple key processes including energy metabolism disorders, oxidative stress, blood-brain barrier (BBB) injury, and neuroinflammation, all of which interact to drive disease progression. Lactylation, a novel epigenetic regulatory mechanism discovered in 2019, provides a fresh perspective for HACE research.

This study integrates the latest research findings on the pathophysiology of HACE, lactate metabolism, and the role of lactylation in hypoxia-related diseases (such as cancer and ischemic-hypoxic diseases). It focuses on analyzing the potential molecular mechanisms of lactylation in HACE, including its regulation of the HIF-1α/NF-κB axis, inflammation, and metabolism, and discusses existing lactylation regulation strategies.

In HACE, hypoxia-driven glycolysis elevates lactate, promoting protein lactylation (e.g., NuRD complex in microglia, which is correlated with proinflammatory cytokines). Lactylation may regulate HIF-1α/NF-κB axis, inflammation, and metabolism in HACE pathogenesis. Currently, methods such as the inhibition of lactate dehydrogenase (LDH) /monocarboxylate transporters and the use of histone deacetylase inhibitors have been proven effective in regulating lactylation.

Lactylation is a key link connecting metabolic disorders and neuroinflammation in HACE. However, the dual role of lactate in neuroprotection and neuroinjury under hypoxic conditions still requires further exploration. Future research should focus on deciphering the molecular networks related to HACE and developing precise intervention strategies to provide new directions for HACE treatment.

Lactate, generated through glycolysis, plays a dual role as both a metabolic substrate and a signalling molecule, influencing cellular functions in pathophysiological scenarios. Protein lactylation, a recently identified form of post-translational modification mediated by lactate, has garnered significant and increasing attention. Globally, hepatic disorders pose a significant public health burden, frequently involving disruptions in glucose metabolism and consequent lactate buildup.

This comprehensive review examines the discovery, regulatory mechanisms and pathogenic roles of lactylation in diverse liver disorders, while critically evaluating emerging lactylation-targeted therapeutics to guide future translational research.

Lactylation modifications play a pivotal role in various pathophysiological processes, including hepatic inflammation, liver fibrosis, ischaemic injury, tumour growth and metastasis.

Modulation of lactylation pathways, coupled with pharmacological control of lactate synthesis and shuttling, emerges as a strategic approach to liver disease therapeutics.

Lactylation, a new epigenetic modification, is an important way in which lactate exerts physiological functions. There is a close relationship between increased lactylations caused by lactate and glycolysis, which can interact and play a role in disease through lactate as an intermediate mediator. Current research on lactylations has focused on histone lactylation, but non-histone lactylation also has greater research potential. Due to the ubiquity of lactate modifications in mammalian cells, an increasing number of studies have found that lactate modifications play important roles in tumour cell metabolism, gene transcription and immunity.

A systematic literature search was carried out using search key terms and synonyms. Full-paper screening was performed based on specific inclusion and exclusion criteria.

Many literatures have reported that the lactylation of protein plays an important role in human diseases and is involved in the occurrence and development of human diseases.

This article summary the correlation between lactylation and glycolysis, histones and non-histone proteins; the relationship between lactonation modifications and tumour development; and the current existence of lactylation-related inhibitors, with a view to provide new basic research ideas and clinical therapeutic tools for lactylation-related diseases.