The structure of reptilian hard (beta)-keratins, their nucleotide and amino acid sequence, and the organization of their genes are presented. These 13-19 kDa proteins are basic, rich in glycine, proline and serine, and different from cytokeratins. Their mRNAs are expressed in beta-cells. The central part of beta-keratins (this region has been previously termed 'core-box' and is peculiar of all sauropsid proteins) is composed of two beta-folded regions and shows a high identity with avian beta-keratins. This central part present in all beta-keratins, including feather keratins, is the site of polymerization to build the framework of beta-keratin filaments. Beta-keratins appear cytokeratin-associated proteins. Their central region might have originated in an ancestral glycine-rich protein present in stem reptiles from which beta-keratins evolved and diversified into reptiles and birds. Stem reptiles of the Carboniferous period might have possessed glycine-rich proteins derived from exons/domains corresponding to the variable, glycine-rich region of cytokeratins. Beta-keratins might have derived from a gene coding for small glycine-rich keratin-associated proteins. The glycine-rich regions evolved differently in the lineage leading to modern reptiles and birds versus that leading to mammals. In the reptilian lineage some amino acid regions produced by point mutations and amino acid changes might have given rise to originate the central beta-pleated region. The latter allowed the formation of filamentous proteins (beta-keratins) associated with intermediate filament keratins and replaced them in beta-keratin cells. In the mammalian lineage no beta-pleated region was generated in their matrix proteins, the glycine-rich keratin-associated proteins. The latter evolved as glycine-tyrosine-rich, sulphur-rich, and ultra-sulphur-rich proteins that are used for building hairs, horns and nails. © 2007 The Authors Journal compilation © 2007 Blackwell Munksgaard.