Figure 5.

Skin lipid alteration in skin conditions showing epidermal barrier dysfunction. (a) Skin lipids are composed of ceramides, free fatty acids, and cholesterol. Abnormalities in lipid composition, transport, and extracellular organization induce abnormal lipid organization. Most of the reports are related to abnormalities in ceramides, which are associated with ichthyoses, ichthyosis syndromes, and atopic dermatitis (AD). Loss-of-function mutations in ABCA12 (ATP-binding cassette transporter A12) cause harlequin ichthyosis, the most severe phenotype of autosomal recessive congenital ichthyosis (ARCI). Loss-of-function mutations in NIPAL4 (NIPA like domain containing 4), CYP4F22, ALOX12B and ALOXE3, PNPLA1 (Patatin-like phospholipase domain-containing lipase 1), and ABHD5 (α/β hydrolase domain-containing protein 5) also cause ARCI. (b) Not much has been reported about the association between altered synthesis of free fatty acid/cholesterol and skin barrier dysfunction. Loss-of-function mutations in ELOVL4 (fatty acid elongase 4) and FATP4 (fatty acid transport protein 4) reduce very long-chain (VLC) or LC fatty acids and cause neurocutaneous disorder (characterized by ichthyosis, seizures, spasticity, intellectual disability, and ichthyosis) and ichthyosis prematurity syndrome, respectively. Although loss-of-function mutations in NSDHL (NADP-dependent steroid dehydrogenase-like) inhibit cholesterol synthesis and cause CHILD syndrome (Congenital Hemidysplasia with Ichthyosiform Erythroderma and Limb Defects), cholesterol depletion is not considered as adequate to induce atopic dermatitis-like alteration in the absence of Th2 cytokines.