ALDH9A1 is a cytosolic NAD+-dependent aldehyde dehydrogenase that catalyzes the oxidation of aldehydes to carboxylic acids with broad substrate specificity 1. The enzyme exhibits highest catalytic efficiency toward γ-trimethylaminobutyraldehyde and functions as a tetrameric protein with a unique inter-domain linker structure not observed in other ALDH family members 1. Beyond canonical aldehyde metabolism, ALDH9A1 generates gamma-aminobutyric acid (GABA) in hepatocellular carcinoma and metabolizes polyamine-derived aldehydes, including 3-aminopropanal and acrolein 2, 3. In cancer contexts, ALDH9A1 exhibits context-dependent roles. In hepatocellular carcinoma, ALDH9A1-derived GABA activates Wnt/β-catenin signaling to promote metastasis 2, while in clear cell renal cell carcinoma and prostate cancer, it functions as a tumor suppressor, with downregulation promoting lipid accumulation and proliferation 4, 5. In cardiovascular disease, increased ALDH9A1 expression associates with reduced calcific aortic valve disease risk through immune modulation, potentially shifting macrophages toward anti-inflammatory M2 phenotypes 6. Clinically, ALDH9A1 deficiency causes synthetic lethality with Fanconi anemia pathway mutations, nominating polyamine-derived aldehydes as endogenous DNA damaging agents in hematologic disease 3. These findings establish ALDH9A1 as a metabolic regulator with distinct therapeutic implications across malignant and cardiovascular pathologies.