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Peer-reviewedCC BYMolecular Biomedicine

Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets

  • Xiuping Wang1,2
  • Cheng Liu3
  • Yue Chen2
  • Yuqing Fang1
  • J N Li1
  • Yu Liu4,2
  • Yu Pan2
  • Suya Bao2
  • Xiwen Wang1,2
  • Yi Liu4,2
  • Hengwei Liu5
5 affiliations
  1. 1Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
  2. 2Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China
  3. 3Department of Gynecology and Obstetrics, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China
  4. 4Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected]
  5. 5Department of Obstetrics and Gynecology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China. [email protected]
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Abstract

The paradigm shift of lactate from a mere metabolic byproduct to a pleiotropic signaling molecule, coupled with the discovery of lactylation, provides a crucial framework for understanding how metabolic reprogramming drives systemic pathology. In this review, we systematically delineate the dynamic equilibrium of lactate homeostasis and the evolution of the lactate shuttle theory, exploring its multidimensional roles as a metabolic substrate, signal transducer, and immunomodulator. Furthermore, we summarize how lactylation orchestrates diverse pathophysiological processes across major organ systems, including metabolic dysfunction and fibrosis in the cardiovascular system, neuroinflammation and apoptosis in the central nervous system, and microenvironment-driven injury across the respiratory, digestive, and urinary tracts. Notably, we highlight the female reproductive system as a unique physiological model for investigating metabolic-epigenetic crosstalk, detailing how histone and non-histone lactylation contribute to the progression of various gynecological pathologies and critical reproductive processes. Finally, we evaluate the clinical translational potential of lactate-related biomarkers and lactylation-targeted therapeutics. Ultimately, this comprehensive framework underscores lactate and its mediated modifications as fundamental epigenetic regulators of cellular function and promising pharmacological targets for precision medicine.

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Cite

BibTeXRIS
BibTeX
@article{wang2026lactate,
  title = {{Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets}},
  author = {Xiuping Wang and Cheng Liu and Yue Chen and Yuqing Fang and J N Li and Yu Liu and Yu Pan and Suya Bao and Xiwen Wang and Yi Liu and Hengwei Liu},
  journal = {Molecular Biomedicine},
  year = {2026},
  month = may,
  doi = {10.1186/s43556-026-00472-x},
  url = {https://doi.org/10.1186/s43556-026-00472-x},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Lactate and lactylation: mechanisms, function, diseases, and therapeutic targets
AU  - Xiuping Wang
AU  - Cheng Liu
AU  - Yue Chen
AU  - Yuqing Fang
AU  - J N Li
AU  - Yu Liu
AU  - Yu Pan
AU  - Suya Bao
AU  - Xiwen Wang
AU  - Yi Liu
AU  - Hengwei Liu
PY  - 2026
DA  - 2026/05/20
JO  - Molecular Biomedicine
DO  - 10.1186/s43556-026-00472-x
UR  - https://doi.org/10.1186/s43556-026-00472-x
AB  - The paradigm shift of lactate from a mere metabolic byproduct to a pleiotropic signaling molecule, coupled with the discovery of lactylation, provides a crucial framework for understanding how metabolic reprogramming drives systemic pathology. In this review, we systematically delineate the dynamic equilibrium of lactate homeostasis and the evolution of the lactate shuttle theory, exploring its multidimensional roles as a metabolic substrate, signal transducer, and immunomodulator. Furthermore, we summarize how lactylation orchestrates diverse pathophysiological processes across major organ systems, including metabolic dysfunction and fibrosis in the cardiovascular system, neuroinflammation and apoptosis in the central nervous system, and microenvironment-driven injury across the respiratory, digestive, and urinary tracts. Notably, we highlight the female reproductive system as a unique physiological model for investigating metabolic-epigenetic crosstalk, detailing how histone and non-histone lactylation contribute to the progression of various gynecological pathologies and critical reproductive processes. Finally, we evaluate the clinical translational potential of lactate-related biomarkers and lactylation-targeted therapeutics. Ultimately, this comprehensive framework underscores lactate and its mediated modifications as fundamental epigenetic regulators of cellular function and promising pharmacological targets for precision medicine.
SN  - 2662-8651
ER  -