A barrier to water loss is vital to maintaining life on dry land. Formation of the mammalian
skin barrier requires both the essential fatty acid linoleate and the two lipoxygenases 12R-
lipoxygenase (12R-LOX) and epidermal lipoxygenase-3 (eLOX3), although their roles are
poorly understood. Linoleate occurs in O-linoleoyl-ω-hydroxyceramide, which, after
hydrolysis of the linoleate moiety, is covalently attached to protein via the free ω-hydroxyl of
the ceramide, forming the corneocyte lipid envelope, a scaffold between lipid and protein …