Diagrammatic representation of adult skin. The basement membrane separates the dermis (primarily consisting of fibroblasts, elastin and collagen) and the overlying epidermis. The epidermis comprises four distinct layers, basal, spinous, granular and the stratum corneum, all arising from basal stem cells. Cellular integrity and communication is maintained via a variety of intercellular junctions. These comprise tight junctions (1), adherens junctions (2), desmosomes (3) and gap junctions (4), of which desmosomes are the most abundant while tight junctions are confined to the second granular layer. The stratum corneum comprises anucleate keratinocytes which have undergone terminal differentiation. This results in the production of an insoluble protein cellular matrix (the cornified envelope), surrounded by a lipid capsule embedded within a network of non-polar lipid. The cornified envelope comprises numerous proteins including involucrin, envoplakin, periplakin, filaggrin, loricrin, SPRRs and LEPs (see inset, reviewed in Kalinin et al. 2001).