Lysine lactylation in diseases: beyond histone lactylation

TL;DR

This paper reviews how lactylation, a protein modification, affects various diseases beyond its initial role in gene regulation.

Contribution

The paper systematically explores the role of lysine lactylation in functional proteins across multiple disease contexts.

Findings

Lysine lactylation extends beyond histones to regulate functional proteins in disease processes.

Kla modifications influence both transcription and direct protein function in biological processes.

The review identifies Kla's role in inflammatory, infectious, neurological, cardiovascular, and oncological diseases.

Abstract

Lactylation, a recently identified post-translational modification, was initially characterized as lysine residue modification in histone subunits that regulates gene transcription via epigenetic mechanisms. Elevated intracellular lactate has been shown to drive histone lysine lactylation (Kla), establishing its association with disease pathogenesis. Emerging evidence reveals that Kla modifications extend beyond histones to transcriptional regulators and cytoplasmic functional proteins. Unlike the broad transcriptional regulation mediated by histone lactylation, Kla modifications of functional proteins exert regulatory effects through both specific transcriptional modulation and direct functional alteration of target proteins, thereby precisely controlling biological processes. This review systematically examines the pathological implications of Kla modifications of functional proteins across multiple disease contexts, including inflammatory disorders, infectious diseases, neurological or cardiovascular pathologies, and oncological conditions. Our synthesis provides mechanistic insights into disease-associated Kla networks, facilitating therapeutic target discovery and pharmacological intervention strategies.

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