Emerging importance of ALDH2 in liver diseases and its potential therapeutic role.

Acetaldehyde dehydrogenase 2 (ALDH2) is an essential metabolic enzyme in mitochondria, responsible for eliminating acetaldehyde and other toxic aldehydes. In the liver, ALDH2 not only has metabolic regulatory functions, but is also closely related to the occurrence and development of various liver diseases. In recent years, studies have demonstrated that the abnormal expression or genetic polymorphism of ALDH2 may be involved in the progression of alcohol-associated liver disease (ALD), metabolic dysfunction-associated steatotic liver disease (MASLD), liver fibrosis, toxin-induced liver injury, hepatocellular carcinoma (HCC) and liver ischemia-reperfusion injury (IRI) by triggering acetaldehyde accumulation and oxidative stress, activating inflammatory response mechanisms and affecting metabolic processes. Therefore, it is of great significance to reveal the key regulatory mechanisms and roles of ALDH2 and its mediated related signaling pathways in liver diseases. Currently, the discovery and development of drugs targeting ALDH2 are receiving increasing attention, and several modulators of ALDH2 have been identified, providing promising directions for the clinical treatment of liver diseases. This review aims to summarize the biochemical and biological functions of ALDH2, as well as its role in liver diseases, and explore its potential and application prospects as a therapeutic target, which will help develop therapeutic strategies for liver diseases.