Aldehyde dehydrogenase family 3 member A2

ALDH3A2 (aldehyde dehydrogenase family 3 member A2) is a cytoplasmic enzyme that catalyzes oxidation of medium and long-chain aliphatic aldehydes to their corresponding fatty acids, with particular activity on substrates ranging from 6 to 24 carbons. It plays a key role in lipid metabolism, including conversion of hexadecenal to hexadecenoic acid during sphingosine 1-phosphate degradation (UniProt: P51648).

The protein is constitutively expressed across tissues involved in lipid homeostasis. Loss-of-function mutations in ALDH3A2 cause Sjögren-Larsson syndrome, an autosomal recessive neurocutaneous disorder characterized by intellectual disability, spastic paralysis, and ichthyosis (UniProt: P51648). These disease features highlight the importance of aldehyde detoxification in neurological and dermatological function.

ALDH3A2 is upregulated in Alzheimer's disease brain tissue compared to age-matched controls (mean log2 fold-change: 0.36 across two subcellular fractions; Chaparral AD proteomics). This elevation may reflect altered lipid metabolism or increased oxidative stress burden in AD pathology, though the functional significance of ALDH3A2 upregulation in neurodegeneration requires further investigation.