Lysine l-Lactylation: Bridging Metabolism, Chromatin and Disease.

Authors

Anoosha Malik, Muhammad Dilawar, Junguang Liao, Jie Zheng, Qitao Qian, Ming Xu, Sisi Lin, Xiaobo Zhu, Qiuwei Ge, Limin Jin, Guiqian Chen

Published in

Cell proliferation. Pages e70262. Jul 12, 2026. Epub Jul 12, 2026.

Abstract

Lysine L-lactylation (K_L-la) is a newly identified metabolite-derived post-translational modification that directly bridges cellular metabolic states to chromatin regulation and protein function. Mounting evidence shows that K_L-la has pivotal roles in transcription regulation and diverse cellular processes and is implicated in multiple pathophysiological conditions. This review comprehensively examines K_L-la across both histone and non-histone substrates in biology and disease. We first illustrate the historical development of K_L-la and distinguish it from its isomers. We then delineate the enzymes regulating K_L-la, examine its crosstalk with other PTMs, and discuss its roles in cell signalling and other biological processes. Particular emphasis is placed on mechanisms through which K_L-la contributes to various human diseases such as cancer, viral infections, neurodegenerative disorders, cardiovascular conditions, metabolic abnormalities and immune dysregulation. Finally, we provide an in-depth analysis of emerging therapeutic strategies targeting K_L-la and highlight future directions for translating mechanistic insights into clinical applications.

PMID:
42437658
Bibliographic data and abstract were imported from PubMed on 13 Jul 2026.

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