The dual faces of lactylation: From post-translational modification to disease regulation

Xuyang Wang; Jiageng Tang; Shuyu Zhang; Xu Chen; Jie Zhang; Yi Fu

doi:10.1016/j.jpha.2026.101589

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Xuyang Wang, Jiageng Tang, Shuyu Zhang, Xu Chen, Jie Zhang, Yi Fu. The dual faces of lactylation: From post-translational modification to disease regulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101589

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Xuyang Wang, Jiageng Tang, Shuyu Zhang, Xu Chen, Jie Zhang, Yi Fu. The dual faces of lactylation: From post-translational modification to disease regulation[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2026.101589

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The dual faces of lactylation: From post-translational modification to disease regulation

doi: 10.1016/j.jpha.2026.101589

Xuyang Wang^a,b,
Jiageng Tang^a,b,
Shuyu Zhang^b,
Xu Chen^a,b,
Jie Zhang^a,b,
Yi Fu^{a,b
,
,}

a. Department of Nephrology, The First Affiliated Hospital of Shandong First Medical University, Jinan, 250014, China;
b. Biomedical Sciences College & Shandong Medicinal Biotechnology Centre, Shandong First Medical University & Shandong Academy of Medical Sciences, Key lab for Biotech-Drugs of National Health Commission; Key Lab for Genetic Engineering and Synthetic Biology of Shandong Province, Ji’nan, Shandong, 250117, China

Funds:

This work was funded by the National Natural Science Foundation of China (Grant No.: 82200809), the Taishan Scholars Program and the Youth Innovation Team Plan in Colleges and Universities of Shandong Province (2023KJ185) and the Natural Science Foundation of Shandong Province (Grant Nos.: ZR2022QH176, ZR2022QC245, and ZR2024MB044). The images in this review were created with Figdraw.

Received Date: Jul. 11, 2025
Accepted Date: Feb. 14, 2026
Rev Recd Date: Feb. 13, 2026
Available Online: Feb. 28, 2026

Abstract

Abstract

Lactate, long regarded as the terminal product of glycolysis, is now recognized as a signaling metabolite that shapes diverse physiological and pathological processes. Lysine lactylation, a recently identified post-translational modification (PTM), has emerged as a key regulator of disease onset and progression. Acting as a double-edged sword, lactylation can either promote pathogenic signaling or facilitate tissue repair, depending on cellular context. These opposing actions highlight its potential as a precise therapeutic target. In this review, we examine the functions of lactate recognition proteins that mediate lactate uptake, transport, and lactylation-associated enzymatic activity. We further detail how histone and non-histone lactylation regulate essential biological processes, including glycolysis-linked cellular functions, RNA modification, macrophage polarization, and cell-fate determination. Finally, we discuss the relationship between lactylation and other modifications, such as acetylation, and provide a forward-looking perspective on the pathophysiological significance of lactylation.
- lactate,
- lactylation,
- metabolism,
- inflammation,
- cancer

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References(144)

References

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