Keratinization

Keratinization, or cornification, is the biological process by which keratinocytes mature and form the epidermal outer barrier. It occurs predominantly in the epidermis of the skin, but similar processes occur in mucosal epithelia. The process begins in the stratum basale, where basal keratinocytes proliferate. As they move outward into the stratum spinosum and stratum granulosum, cells undergo terminal differentiation. In the granulosum, keratohyalin granules release profilaggrin, which is processed to filaggrin and helps aggregate keratin filaments made of keratin 1 and 10. Concurrently, lamellar bodies release lipid-rich lamellae that assemble into the intercellular lipid matrix, contributing to barrier function.

The epidermal cells form a cross-linked cornified envelope, composed of structural proteins such as involucrin, loricrin, small proline-rich proteins, and transglutaminase-catalyzed cross-links. The cells later lose their nuclei and organelles, becoming corneocytes. These enucleated cells are shed in a process called desquamation, maintaining a protective outer layer known as the stratum corneum. The whole maturation cycle from basal cell to corneocyte turnover takes about a month in healthy adult skin.

Keratinization is regulated by signaling pathways including Notch and epidermal growth factor receptor signaling, and is modulated by retinoids and other factors. Impaired keratinization can lead to disorders such as ichthyosis or psoriasis, whereas hyperkeratosis reflects excessive keratinization or slowed desquamation. Proper keratinization is essential for barrier function against dehydration, pathogens, and mechanical stress.