# Protein lactylation in metabolic dysfunction-associated steatotic liver disease: a mechanistic review

## TL;DR

This review explores how protein lactylation, a new type of chemical modification, influences liver disease progression and could lead to new treatments.

## Contribution

The paper introduces a novel conceptual framework linking protein lactylation to MASLD progression and potential precision therapies.

## Key findings

- Protein lactylation connects metabolic changes to liver disease progression.
- Dysregulation of lactylation occurs in hepatocytes, hepatic stellate cells, and immune cells during MASLD.
- Targeting the lactate-lactylation-gene expression axis may offer new therapeutic strategies.

## Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver disorder with limited therapeutic options. While its pathogenesis is complex, the underlying molecular drivers remain incompletely understood. Recently, protein lactylation, a novel lactate-derived post-translational modification (PTM), has emerged as a key regulator linking metabolic reprogramming to cellular function. This review elucidates the pivotal roles of protein lactylation throughout the progression of MASLD, from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and hepatocellular carcinoma, establishing a conceptual framework centered on the “lactate-lactylation-gene expression” axis and examining its dysregulation across hepatocytes, hepatic stellate cells, and immune cells throughout MASLD. Furthermore, we discuss emerging therapeutic strategies targeting the axis, aiming to provide a theoretical foundation for the development of precision medicine for MASLD.