Epidermis-type lipoxygenase 3 (ALOXE3)

Epidermis-type lipoxygenase 3 (ALOXE3) is a non-heme iron enzyme classified within the lipoxygenase family, but distinct in its catalytic function: instead of directly oxygenating polyunsaturated fatty acids like classical lipoxygenases, it acts as a hydroperoxide isomerase converting fatty acid hydroperoxides into specific hepoxilin-type epoxyalcohols and ketones. ALOXE3’s principal physiological role is in the epidermis, where it is essential for the formation of the lipid envelope of corneocytes necessary for water barrier function; mutations in the gene cause congenital ichthyosis. Beyond the skin, recent research implicates ALOXE3 in adipocyte differentiation via PPARγ activation, fasting-induced improvements in hepatic metabolism, and modulation of neuronal excitability and seizure threshold via arachidonic acid metabolism. Therapeutic interest focuses on metabolic syndrome, diabetes, skin barrier disorders, and neuroinflammatory pain, though no approved drugs directly target ALOXE3 as yet

Other names

Hydroperoxide isomerase ALOXE3eLOX3Epidermal LOX-3Epidermal lipoxygenase-3Epidermis-type lipoxygenase 3Hydroperoxy dehydratase ALOXE3Hydroperoxy icosatetraenoate dehydrataseHydroperoxy icosatetraenoate isomeraseARCI3Lamellar ichthyosis 5LI5arachidonate lipoxygenase 3

Drugs or gene therapy enhancing ALOXE3 (e.g., adeno-associated virus, trehalose analogues) increase ALOXE3 activity to promote PPARγ-mediated signaling, reduce inflammation, restore barrier function, and modulate neuronal excitability