Hornerin is a component of the epidermal cornified cell envelopes.

A single-nucleotide polymorphism within the gene encoding hornerin (HRNR) has recently been linked with atopic dermatitis (AD) susceptibility. HRNR shares features with filaggrin, a key protein for keratinocyte differentiation, but conflicting reports have been published concerning its expression in the epidermis, and its role is still unknown. To analyze HRNR expression and function in the epidermis, anti-HRNR antibodies were produced and used in Western blot analysis and immunohistochemical, confocal, and immunoelectron microscopy analyses of human skin and of cornified cell envelopes purified from plantar stratum corneum. We also tested whether HRNR was a substrate of transglutaminases. In the epidermis, HRNR was detected at the periphery of keratohyalin granules in the upper granular layer and at the corneocyte periphery in the whole cornified layer. Detected in Western blot analysis as numerous bands, HRNR was relatively insoluble and only extracted from epidermis with urea and/or reducing agents. The presence of HRNR in the purified envelopes was confirmed by immunoelectron microscopy and by Western blot analysis after V8-protease digestion. HRNR was shown to be a substrate of transglutaminase 3. These data demonstrate that HRNR is a component of cornified cell envelopes of human epidermis. Its reduced expression in AD may contribute to the epidermal barrier defect observed in the disease.