Keratin: A Journey of Three Decades

During the past three decades, major progress has been made in our understanding of the processes which lead to the formation of a keratinized epidermis in normal and pathologic situations. Stimulated by clinical studies of exfoliative dermatitis and related diseases, a series of investigations have been performed which proved initially that the pathways and controls of epidermal protein synthesis were equivalent to protein synthetic pathways in all other tissues of the body. Keratin was identified as not only an insoluble protein which makes up the vast majority of the intracellular protein in the stratum corneum, but as a member of the intermediate filament family of cytoskeletal proteins. Of all such proteins, the keratins are most complex, occurring in two families separable on the basis of size, structure and isoelectric point. The keratin intermediate filaments are heteropolymers of two paired components, one from each family. The pairs of keratins which form the intermediate filaments in basal and differentiated layers of epidermis and other epithelia have been defined and antibodies to specific keratins are now being used for diagnostic purposes. Sophisticated biochemical, physicochemical, and molecular biologic studies have led to complete definitions of almost all the epithelial keratin molecules and to cloning of their genes. These genes are currently being used in analyses of control of keratin expression and definition of the specific abnormalities associated with “keratinopathies” including epidermolysis bullosa simplex and epidermolytic hyperkeratosis.