To date, positional cloning and homozygosity mapping of families with ARCI have identified disease-associated mutations in seven genes: ABCA12, ALOX12B, ALOXE3, CYP4F22, ICHTHYIN, PNPLA1, and TGM1. The reported molecular mechanisms underlying disease development are related to defects in epidermal lipid pathways that interfere with terminal keratinocyte differentiation and skin barrier function. The gene discussed is PNPLA1; the disease is autosomal recessive congenital ichthyosis.