Differentially expressed late constituents of the epidermal cornified envelope

Barrier activity of skin and internal barrier-forming epithelial linings ar e conferred by a lipid-corneocyte structure (stratum corneum In skin). The integrity of the corneocytes depends on the outer cornified envelope and is essential for maintenance of barrier function. During epidermal developmen t and differentiation, proteins are sequentially incorporated into the enve lope via action of epidermal transglutaminases in a well documented process . However, recent knockouts of major cornified envelope constituents have f ailed to disrupt barrier function significantly, suggesting that additional unidentified components are involved. We report a new gene cluster in the epidermal differentiation complex at human 1q21 encoding a family of 18 pro teins that are substrates for epidermal transglutaminases. These proteins i ncorporate into the cornified envelope late in development and late in the process of envelope maturation during epidermal differentiation. The genes cluster within the epidermal differentiation complex according to expressio n pattern, i.e., epidermally expressed proteins cluster together while prot eins from internal barrier-forming epithelia also cluster. We propose that these proteins modulate barrier activity over the surface of the animal, in a manner analogous to that proposed for the well characterized cornified e nvelope precursors, the small proline-rich proteins. To emphasize the incor poration of these proteins late in envelope assembly, we call the human pro teins late envelope proteins.