Editorial

Interwoven control of histone lactylation: metabolic enzymes LDHA/ACSS2 couple with epigenetic writer KAT2A

¹ Zhejiang Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang Key Laboratory of Frontier Medical Research on Cancer Metabolism, Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310029, PR China
² Institute of Fundamental and Transdisciplinary Research, Cancer Center, Zhejiang University, Hangzhou, Zhejiang 310029, PR China
³ The Center for Translational Research, The Second Affiliated Hospital and Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang 310029, PR China

^* Corresponding author: This email address is being protected from spambots. You need JavaScript enabled to view it.

Received: 22 May 2025
Accepted: 10 December 2025

Abstract

Histone lactylation is critically involved in the regulation of gene expression and the modulation of diverse cellular processes in both normal and tumor cells. A recent study by Zhu et al. [Cell Metab. 37, 361–376] demonstrated that ACSS2 functions as a bona fide lactyl-CoA synthetase, converting lactate into lactyl-CoA. In response to elevated aerobic glycolysis and EGFR activation, ERK-mediated phosphorylation drives the nuclear translocation of ACSS2, promoting the formation of the ACSS2–KAT2A complex. KAT2A utilizes ACSS2-derived lactyl-CoA and acts as a lactyltransferase to promote histone lactylation, gene expression, tumor growth, and immune evasion.