Aldh3a2, or aldehyde dehydrogenase 3 family member A2, catalyzes the oxidation of long-chain aliphatic aldehydes to fatty acid [1,2]. It is involved in lipid metabolic, GSH metabolic, phospholipid metabolic, and aldehyde metabolic pathways [1]. Mutations in Aldh3a2 are associated with Sjögren-Larsson syndrome, a neuro-ichthyotic condition due to fatty aldehyde dehydrogenase (FALDH) deficiency [4,5,6].

In ovarian cancer, knockout of Aldh3a2 increased ferroptosis sensitivity, while overexpression attenuated it, suggesting that Aldh3a2 affects ovarian cancer cell survival by altering ferroptosis sensitivity through influencing relevant metabolic processes [1]. In acute myeloid leukemia (AML), leukemic cells depend on Aldh3a2 to prevent cellular oxidative damage, and Aldh3a2 inhibition is synthetically lethal with glutathione peroxidase-4 (GPX4) inhibition [2]. In clear cell renal cell carcinoma (ccRCC), miR-1182-mediated ALDH3A2 inhibition promotes lipid accumulation and tumor progression by activating the PI3K-AKT pathway [3].

In conclusion, Aldh3a2 plays crucial roles in preventing oxidative damage, regulating ferroptosis, and influencing lipid metabolism in various diseases such as ovarian cancer, AML, and ccRCC. Gene knockout studies in relevant disease models have revealed its important functions in these disease-related biological processes, providing potential therapeutic strategies for these malignancies [1,2,3].