keratohyalin

Keratohyalin refers to a group of cytoplasmic proteins found in keratinocytes of the epidermis, most notably within the keratohyalin granules of the stratum granulosum. These granules appear during late differentiation of keratinocytes and are visible histologically as basophilic inclusions. Keratohyalin material is rich in profilaggrin, a large precursor of filaggrin, and other associated proteins.

During epidermal differentiation, profilaggrin is proteolytically processed within keratohyalin granules to filaggrin monomers. Filaggrin binds to keratin intermediate filaments, promoting their aggregation and facilitating the collapse of keratinocytes into flattened corneocytes. This process aids in the formation of the cornified cell envelope and the maturation of the stratum corneum. Degradation of filaggrin also yields natural moisturizing factors, including amino acids, contributing to skin hydration.

Clinical relevance: Mutations in the FLG gene, encoding profilaggrin/filaggrin, reduce filaggrin production and are associated with ichthyosis vulgaris and atopic dermatitis, reflecting a compromised skin barrier and altered water retention.

Overall, keratohyalin plays a central role in epidermal differentiation and barrier formation by storing profilaggrin in granules and enabling its processing to filaggrin, which in turn organizes keratin networks and supports stratum corneum integrity.