Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies

ABSTRACT Lactylation, a recently identified post‐translational modification, represents a groundbreaking addition to the epigenetic landscape, revealing its pivotal role in gene regulation and metabolic adaptation. Unlike traditional modifications, lactylation directly links metabolic intermediates,...

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Main Authors: Xi Chen, Yixiao Yuan, Fan Zhou, Lihua Li, Jun Pu, Yong Zeng, Xiulin Jiang
Format: Article
Language:English
Published: Wiley 2025-06-01
Series:MedComm
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Online Access:https://doi.org/10.1002/mco2.70226
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author Xi Chen
Yixiao Yuan
Fan Zhou
Lihua Li
Jun Pu
Yong Zeng
Xiulin Jiang
author_facet Xi Chen
Yixiao Yuan
Fan Zhou
Lihua Li
Jun Pu
Yong Zeng
Xiulin Jiang
author_sort Xi Chen
collection DOAJ
description ABSTRACT Lactylation, a recently identified post‐translational modification, represents a groundbreaking addition to the epigenetic landscape, revealing its pivotal role in gene regulation and metabolic adaptation. Unlike traditional modifications, lactylation directly links metabolic intermediates, such as lactate, to protein function and cellular behavior. Emerging evidence highlights the critical involvement of lactylation in diverse biological processes, including immune response modulation, cellular differentiation, and tumor progression. However, its regulatory mechanisms, biological implications, and disease associations remain poorly understood. This review systematically explores the enzymatic and nonenzymatic mechanisms underlying protein lactylation, shedding light on the interplay between cellular metabolism and epigenetic control. We comprehensively analyze its biological functions in normal physiology, such as immune homeostasis and tissue repair, and its dysregulation in pathological contexts, including cancer, inflammation, and metabolic disorders. Moreover, we discuss advanced detection technologies and potential therapeutic interventions targeting lactylation pathways. By integrating these insights, this review aims to bridge critical knowledge gaps and propose future directions for research. Highlighting lactylation's multifaceted roles in health and disease, this review provides a timely resource for understanding its clinical implications, particularly as a novel target for precision medicine in metabolic and oncological therapies.
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spelling doaj-art-b530af5bc19f4c5c80f6a0b0dffd88442025-08-20T02:56:34ZengWileyMedComm2688-26632025-06-0166n/an/a10.1002/mco2.70226Lactylation: From Homeostasis to Pathological Implications and Therapeutic StrategiesXi Chen0Yixiao Yuan1Fan Zhou2Lihua Li3Jun Pu4Yong Zeng5Xiulin Jiang6Key Laboratory of Neurological and Psychiatric Disease Research of Yunnan Province The Second Affiliated Hospital of Kunming Medical University Kunming ChinaDepartment of Medicine, UF Health Cancer Center University of Florida Gainesville Florida USADepartment of Hematology the Second Hospital Affiliated to Kunming Medical University Kunming ChinaNHC Key Laboratory of Drug Addiction Medicine Kunming Medical University Kunming ChinaKey Laboratory of Neurological and Psychiatric Disease Research of Yunnan Province The Second Affiliated Hospital of Kunming Medical University Kunming ChinaKey Laboratory of Neurological and Psychiatric Disease Research of Yunnan Province The Second Affiliated Hospital of Kunming Medical University Kunming ChinaDepartment of Medicine, UF Health Cancer Center University of Florida Gainesville Florida USAABSTRACT Lactylation, a recently identified post‐translational modification, represents a groundbreaking addition to the epigenetic landscape, revealing its pivotal role in gene regulation and metabolic adaptation. Unlike traditional modifications, lactylation directly links metabolic intermediates, such as lactate, to protein function and cellular behavior. Emerging evidence highlights the critical involvement of lactylation in diverse biological processes, including immune response modulation, cellular differentiation, and tumor progression. However, its regulatory mechanisms, biological implications, and disease associations remain poorly understood. This review systematically explores the enzymatic and nonenzymatic mechanisms underlying protein lactylation, shedding light on the interplay between cellular metabolism and epigenetic control. We comprehensively analyze its biological functions in normal physiology, such as immune homeostasis and tissue repair, and its dysregulation in pathological contexts, including cancer, inflammation, and metabolic disorders. Moreover, we discuss advanced detection technologies and potential therapeutic interventions targeting lactylation pathways. By integrating these insights, this review aims to bridge critical knowledge gaps and propose future directions for research. Highlighting lactylation's multifaceted roles in health and disease, this review provides a timely resource for understanding its clinical implications, particularly as a novel target for precision medicine in metabolic and oncological therapies.https://doi.org/10.1002/mco2.70226biological significancecancer immunotherapypathologyphysiologyprotein lactylation
spellingShingle Xi Chen
Yixiao Yuan
Fan Zhou
Lihua Li
Jun Pu
Yong Zeng
Xiulin Jiang
Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
MedComm
biological significance
cancer immunotherapy
pathology
physiology
protein lactylation
title Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
title_full Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
title_fullStr Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
title_full_unstemmed Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
title_short Lactylation: From Homeostasis to Pathological Implications and Therapeutic Strategies
title_sort lactylation from homeostasis to pathological implications and therapeutic strategies
topic biological significance
cancer immunotherapy
pathology
physiology
protein lactylation
url https://doi.org/10.1002/mco2.70226
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AT yixiaoyuan lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies
AT fanzhou lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies
AT lihuali lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies
AT junpu lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies
AT yongzeng lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies
AT xiulinjiang lactylationfromhomeostasistopathologicalimplicationsandtherapeuticstrategies