The role of fatty aldehyde dehydrogenase in epidermal structure and function

The epidermal water barrier resides in the stratum corneum (SC) and is dependent on a highly organized network of multi-lamellar membranes comprised of a critical lipid composition. The SC membranes are formed from precursor membranes packaged in cytoplasmic lamellar bodies in the stratum granulosum and delivered to the SC by exocytosis. An abnormal lipid composition of the SC membranes often results in a disrupted water barrier and the clinical appearance of ichthyosis. This cutaneous feature is characteristic of Sjögren-Larsson syndrome (SLS), an inborn error of lipid metabolism caused by deficiency of fatty aldehyde dehydrogenase (FALDH). The contribution of FALDH to normal epidermal function has become increasingly evident with the recognition that this enzyme has an essential role in metabolism of several lipids, including fatty aldehydes and alcohols, ether glycerolipids, isoprenoid alcohols and certain lipids that undergo ω-oxidation, such as leukotriene B4 and very long-chain fatty acids. In the absence of FALDH, the skin produces lamellar bodies that are empty, lack their surrounding vesicle membranes or contain granular contents rather then the usual cargo membranes. These defective organelles also have impaired exocytosis, which results in structurally abnormal, deficient multi-lamellar membranes in the SC and a leaky water barrier. Although the exact biochemical mechanism for the cutaneous pathology is still unclear, studies in SLS demonstrate the critical importance of FALDH for normal epidermal structure and function.