ALDH3A1 (aldehyde dehydrogenase 3 family member A1) is an NAD+-dependent enzyme that oxidizes medium and long chain aldehydes, particularly aromatic aldehydes, into non-toxic fatty acids 1. The enzyme serves dual catalytic and non-catalytic functions, including antioxidant activities and structural roles 1. ALDH3A1 is highly expressed in stomach, lung, keratinocytes, and cornea, comprising about 50% of corneal epithelial soluble proteins where it may protect against UV-induced damage 1. The enzyme plays a critical role in cellular detoxification by metabolizing toxic aldehydes derived from lipid peroxidation, providing resistance against oxidative stress 1. In cancer contexts, ALDH3A1 expression is significantly elevated and correlates with poor prognosis in non-small cell lung cancer (NSCLC) 2. The enzyme promotes tumor proliferation by enhancing glycolysis while suppressing oxidative phosphorylation through activation of the HIF-1α/LDHA pathway 2. ALDH3A1 also contributes to drug resistance in cancer cells by generating metabolic vulnerabilities - its upregulation can induce NADH-reductive stress, making cells susceptible to Complex I inhibition 3. Additionally, ALDH3A1 participates in regulatory feedback loops that promote EGFR-TKI resistance through lactate production 4.