Aldh1a3, an aldehyde dehydrogenase family member, is crucial for oxidizing all-trans-retinal to retinoic acid, participating in various physiological processes in human cells. It has been associated with multiple pathways such as glycometabolism, and is linked to the development, progression, and prognosis of cancers. Genetic models, like gene knockout (KO) or conditional knockout (CKO) mouse models, are valuable tools for studying its functions [3,4].

In pulmonary arterial hypertension (PAH), Aldh1a3 is up-regulated in pulmonary arterial smooth muscle cells (PASMC) from PAH patients. Mice with Aldh1a3 deleted in SMC did not develop hypoxia-induced pulmonary arterial muscularization or pulmonary hypertension. Nuclear Aldh1a3 converts acetaldehyde to acetate to produce acetyl coenzyme A, which acetylates H3K27, regulating genes required for PASMC proliferation and glycolysis [1]. In type 2 diabetes, genetic or pharmacological inhibition of Aldh1a3 in diabetic mice lowers glycemia and increases insulin secretion, suggesting Aldh1a3 inhibition as a therapeutic strategy against β-cell dysfunction [2].

In conclusion, Aldh1a3 plays significant roles in various biological processes and diseases. The use of KO/CKO mouse models has revealed its importance in PAH and diabetes, providing insights into potential therapeutic strategies. Its function in regulating gene expression and metabolism through specific mechanisms offers new directions for understanding disease pathogenesis and developing targeted treatments.