Desmosealin and other components of the epidermal extracellular matrix.

Integrity of the skin is necessary for maintaining body's homeostasis. Barrier function of human skin largely depends on the final product of epidermal cell differentiation, the horny layer, i.e. stratum corneum. As epidermis is constantly in self-renewal, the superficial desquamation is adequately compensated by keratinocyte proliferation in epidermal basal layer. Cohesion in the epidermis depends on the presence of specialized adhering junctions, desmosomes, and their modified version encountered in the horny layer, corneodesmosomes. These structures must be finely regulated to allow a regular flow of differentiating keratinocytes through the epidermal layers and their release at the top of the skin, without compromising tissue resilience and cohesion. Extracellular matrix (ECM) molecules, which fill the inter-keratinocyte spaces in living epidermal layers, are involved in tissue hydration, nutrition, and regulation of cell proliferation and differentiation. In the stratum corneum, extracellular lipids self-organize into multilayered sheets, essential for establishing of the permeability barrier. Desmosealin is a new epidermal proteoglycan, part of the tissue-specific ECM, that shows affinity to the extracellular compartment of desmosomes. This highly glycosylated molecule may play a role in the protection of desmosomes against premature proteolysis of its components, and, thus, in the skin barrier function.