The roles of ABCA12 in epidermal lipid barrier formation and keratinocyte differentiation.

[lamellar ichthyosis]

ATP-binding cassette (ABC ) transporters form a large superfamily of transporters that bind and hydrolyze ATP to transport various molecules across limiting membranes or into vesicles . The ABCA subfamily members are thought to transport lipid materials . ABCA 12 is a keratinocyte transmembrane lipid transporter protein associated with the transport of lipids via lamellar granules . ABCA 12 is considered to transport lipids including ceramides to form extracellular lipid layers in the stratum corneum of the epidermis , which is essential for skin barrier function . ABCA 12 mutations are known to underlie the three major types of autosomal recessive congenital ichthyoses : harlequin ichthyosis , lamellar ichthyosis and congenital ichthyosiform erythroderma . ABCA 12 mutations result in defective lipid transport via lamellar granules in the keratinocytes , leading to ichthyosis phenotypes from malformation of the stratum corneum lipid barrier . Studies on ABCA 12 -deficient bioengineered models have revealed that lipid transport by ABCA 12 is required for keratinocyte differentiation and epidermal morphogenesis . Defective lipid transport due to loss of ABCA 12 function leads to the accumulation of intracellular lipids , including glucosylceramides and gangliosides , in the epidermal keratinocytes . The accumulation of gangliosides seems to result in the apoptosis of Abca 12 (-/-) keratinocytes . It was reported that AKT activation occurs in Abca 12 (-/-) granular-layer keratinocytes , which suggests that AKT activation serves to prevent the cell death of Abca 12 (-/-) keratinocytes . This article is part of a Special Issue entitled The Important Role of Lipids in the Epidermis and their Role in the Formation and Maintenance of the Cutaneous Barrier . Guest Editors : Kenneth R . Feingold and Peter Elias .