ALDH1A1 is a cytosolic aldehyde dehydrogenase that catalyzes the irreversible oxidation of aldehydes to carboxylic acids 123456. Its primary metabolic function involves retinoid metabolism, where it oxidizes retinaldehyde to retinoic acid as the second step in vitamin A metabolism [UniProt]. ALDH1A1 also detoxifies lipid peroxidation products like 4-hydroxynon-2-enal, preventing protein adduct formation and lens opacification 124. In cancer biology, ALDH1A1 has emerged as a critical regulator of tumor progression and therapeutic resistance. ALDH1A1 activity drives prostate cancer metastasis and radioresistance through interplay with androgen and retinoid receptor signaling, with high expression marking metastasis-initiating cells 7. In breast cancer, ALDH1A1 enzymatic activity promotes tumor growth by decreasing intracellular pH, activating NF-κB signaling, and triggering myeloid-derived suppressor cell expansion 8. ALDH1A1 upregulation confers resistance to KRAS inhibitors by suppressing ferroptosis through detoxification of reactive aldehydes and NADH synthesis 9. Similarly, ALDH1A1 expression correlates with chemoresistance in ovarian cancer 10, and an S100A9-ALDH1A1-retinoic acid axis drives brain relapse in EGFR-mutant lung cancer 11. In pancreatic cancer, ALDH1A1 ubiquitination by FBXL12 mediates ferroptosis induction 12.