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<p>Lactylation, as a novel post-translational modification, plays a key role in gene transcription and protein expression, serving as an important link between cellular metabolism and functional regulation. Ferroptosis is a regulatory form of cell death characterized by iron-dependent lipid peroxidation, and its abnormal regulation is closely associated with the onset and progression of various diseases, including tumors, degenerative diseases, and ischemia–reperfusion injury. Recent studies have shown that lactylation can regulate ferroptosis-related pathways and key targets through multiple mechanisms, regulate ferroptosis and thereby influence disease progression. This review first comprehensively summarizes the mechanisms of lactylation and ferroptosis, then systematically reviews the regulatory mechanisms and roles of lactylation in ferroptosis, and finally, we summarize the role of lactylation-regulated ferroptosis in various diseases and its potential as a therapeutic target. The aim is to deepen our understanding of the regulatory mechanisms and roles of lactylation in ferroptosis and to lay the foundation for the development of precision treatment strategies for related diseases.</p>

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Lactylation-regulated ferroptosis: mechanisms, disease associations, and therapeutic strategies

  • 期刊论文

  • 发表日期：

    2026年5月10日

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  • Yun Lei,
  • Si-Qi Ding,
  • Kai-Qiang Li,
  • Xiao Bai,
  • Hao-Zhu Liu,
  • Zhe-Ming Zhao,
  • Dong-Qiu Dai

摘要

Lactylation, as a novel post-translational modification, plays a key role in gene transcription and protein expression, serving as an important link between cellular metabolism and functional regulation. Ferroptosis is a regulatory form of cell death characterized by iron-dependent lipid peroxidation, and its abnormal regulation is closely associated with the onset and progression of various diseases, including tumors, degenerative diseases, and ischemia–reperfusion injury. Recent studies have shown that lactylation can regulate ferroptosis-related pathways and key targets through multiple mechanisms, regulate ferroptosis and thereby influence disease progression. This review first comprehensively summarizes the mechanisms of lactylation and ferroptosis, then systematically reviews the regulatory mechanisms and roles of lactylation in ferroptosis, and finally, we summarize the role of lactylation-regulated ferroptosis in various diseases and its potential as a therapeutic target. The aim is to deepen our understanding of the regulatory mechanisms and roles of lactylation in ferroptosis and to lay the foundation for the development of precision treatment strategies for related diseases.