Cornification Diseases (Skin Cell Death)

Abstract The outermost layer of the skin is formed by the cornified envelope (CE), which is the end product of the process of keratinisation. This forms a barrier that is essential to protect the internal homeostasis of the organism from the external environment. The process of keratinisation proceeds according to a complex and elaborately controlled differentiation programme with the coordinated expression of genes encoding specialised components, enzymes and regulatory molecules. The CE is a specialised structure that replaces the plasma membrane of differentiating keratinocytes and consists of proteins cross‐linked by covalent bonds and lipids to form a scaffold. Understanding of the pathologies associated with defects in CE components will help clarify the molecular mechanisms and the physiological endpoints of keratinisation. Key Concepts The outermost layer of the skin is formed by the cornified envelope (CE). The CE is a specialised structure that replaces the plasma membrane of differentiating keratinocytes. It consists of proteins cross‐linked by covalent bonds and lipids to form a scaffold. The CE is essential to provide the barrier function of the epidermis. The transglutaminase enzymes play a major role in the formation of the CE by catalysing the formation of cross‐links between specific proteins. Mutations in keratin genes cause a wide variety of epidermal and other epithelial disorders. CE lipids contribute in a significant way to the establishment of barrier function of the epidermis by impermeabilising the cornified cell and participating in the organisation of the intercellular lipid lamellae. Defects in proteases result in barrier function abnormalities or skin diseases. The transcription factor p63 is crucial in epidermis formation, maintaining the progenitor‐cell populations that are necessary to sustain epithelial development and morphogenesis.