Keratinisation vs Cornification
Keratinisation and cornification are synonymous terms referring to the same physiological process—the terminal differentiation and programmed cell death of keratinocytes that forms the stratum corneum of the epidermis. 1
Terminology Clarification
The Nomenclature Committee on Cell Death explicitly states that cornification is "also known as 'keratinization' or 'cornified envelope formation'", confirming these are interchangeable terms for the same biological process. 1
Both terms describe the physiological death subroutine occurring in the external layer of the epidermis that generates the stratum corneum, a layer of dead keratinocytes (corneocytes) containing specific proteins and lipids. 1
The term "cornification" is preferred in modern cell death nomenclature because it more accurately describes the formation of the cornified envelope and distinguishes this process from other forms of cell death. 1, 2
Biological Process
Cornification/keratinisation is restricted to keratinocytes and functionally linked to generating the stratum corneum, which provides structural stability, mechanical resistance, elasticity, and water repellence to skin. 1
The process involves synthesis of specific enzymes (caspase-14 and transglutaminases 1,3, and 5) that catalyze crosslinking reactions to form the cornified envelope. 1
Substrate proteins include keratin, filaggrin, loricrin, SPR, involucrin, and SP100, along with lipids (fatty acids and ceramides) that are extruded into extracellular spaces and covalently attached to envelope proteins. 1
Cornification constitutes a bona fide cell death program because, unlike lens epithelium and red blood cells that undergo similar terminal differentiation, corneocytes completely lose the ability to succumb to stress-induced cell death. 1
Biochemical Characteristics
The process can be altered (though not completely blocked) by inhibition of transglutaminases or caspase-14, which are critical enzymes in the cornification pathway. 1
Caspase-14 deficient mice demonstrate altered stratum corneum composition with reduced hydration, increased water loss, and high sensitivity to UV-induced DNA damage, confirming its critical role. 1
Keratinocytes activate anti-apoptotic and anti-necroptotic pathways during terminal differentiation to prevent premature cell death before cornification is complete. 2
Historical Context
Historically, "keratin" referred to all proteins extracted from skin modifications (horns, claws, hooves), but this was later recognized as a mixture of keratins, keratin filament-associated proteins, and other proteins. 3
The term "prekeratin" or "cytokeratin" was previously used for filament-forming proteins from living epidermal layers, while "keratin" was reserved for proteins from the cornified layer—a distinction that is now obsolete. 3
Current nomenclature defines "keratin" as all intermediate filament-forming proteins with specific physicochemical properties produced in any vertebrate epithelia, regardless of whether they are in living or cornified layers. 3
Clinical Relevance
Acitretin normalizes epidermal cell proliferation, differentiation, and cornification in psoriasis and other disorders of keratinization, demonstrating the clinical importance of understanding this process. 1
Disorders of keratinization/cornification include severe congenital ichthyosis, Darier disease, and palmoplantar keratoderma, all involving abnormal terminal differentiation. 1, 4
The British Association of Dermatologists uses "keratinization disorders" and "disorders of cornification" interchangeably when describing conditions affecting this process. 4