Hydroperoxide isomerase (ALOXE3, e-LOX-3) is a non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyses the isomerisation of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into epoxyalcohols (Yu et al. 2003).
In the skin, ALOXE3 acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins, important for the maintenance of the skin permeability barrier and protection against water loss. Loss-of-function mutations in ALOX12B and ALOXE3 represent the second most common cause of autosomal recessive congenital ichthyosis, a hereditary disorder of keratinization (Yu et al. 2005, Wang et al. 2015). Targeted disruption of these genes in mice resulted in neonatal death due to a severely impaired permeability barrier function (Zheng et al. 2011).