All SPRR genes are closely linked within a 300-kb DNA segment on 1q21-q22.Marvin et al. (1992) characterized a cDNA clone corresponding to mRNA abundantly expressed in differentiating squamous cells originally isolated from a rabbit squamous cell library. Small Proline Rich Protein 1B is a 14-kD protein that appears to function as a component of the crosslinked envelope in squamous differentiating cells. Called cornifin, the protein has a high content of proline (31%), glutamine (20%), and cysteine (11%) and contains 13 repeats of an octapeptide (consensus sequence, EPCQPKVP) at its C terminus. In situ hybridization analysis showed that the mRNA is restricted to the suprabasal layers of the epidermis. Crosslinking of the protein appears to be mediated by transglutaminase type I.