Genetic deficiency in 12R-LOX or of the subsequent enzymes in the pathway (eLOX3 [epidermal lipoxygenase-3] and SDR9C7 [short-chain dehydrogenase-reductase family 7 member 9]) results in severe skin barrier disruption, which in common with deficiencies in other barrier genes is neonatal lethal in mice due to uncontrollable transepidermal water loss (22, 23, 24, 25) and causes congenital ichthyosis (scaly skin disease) in humans. Here, ALOXE3 is linked to inherited ichthyosis.