ALDH2 is a mitochondrial aldehyde dehydrogenase required for clearance of toxic aldehydes, including formaldehyde, acetaldehyde, and 4-hydroxynonenal, which are cytotoxic and carcinogenic metabolites inducing DNA damage 1. Beyond its classical role in ethanol metabolism 2, ALDH2 functions as a critical health-promoting enzyme with broader implications for cellular detoxification and mitochondrial homeostasis. Mechanistically, ALDH2 regulates multiple pathways: it promotes PGC-1α-mediated mitochondrial biogenesis and oxidative phosphorylation 3, enhances PAD4 ubiquitination to suppress pathological neutrophil extracellular trap formation 4, and reduces accumulation of toxic aldehyde-protein adducts in brown adipose tissue 5. Post-translational modifications of ALDH2, such as lactylation, can impair its function and promote mitochondrial dysfunction 6. Clinically, the common ALDH2rs671 polymorphism in East Asian populations (~560 million carriers) reduces enzymatic activity and associates with increased susceptibility to multiple diseases: sepsis-induced acute respiratory distress syndrome 4, atherosclerosis and cardiovascular disease 7, obesity, type 2 diabetes, and metabolic dysfunction 5. Paradoxically, ALDH2 inhibition may protect against aortic aneurysm through vascular smooth muscle cell phenotype modulation 8. ALDH2 activators like Alda-1 and AD-9308 show therapeutic promise in preclinical models 35.