The skin is the largest organ of the mammalian body. The outermost layer of mammalian skin, the stratum corneum (SC) of the epidermis, consists of piles of dead corneocytes that are the endproducts of terminal differentiation of epidermal keratinocytes. The SC performs a crucial barrier function of epidermis. Langerhans cells, when activated, extend their dendrites through tight junctions just beneath the SC to capture external antigens. Recently, knowledge of the biology of corneocytes ('corneobiology') has progressed rapidly and many key factors that modulate its barrier function have been identified and characterized. In this review article on the SC, we summarize its evolution, formation, structure and function. Cornification is an important step of SC formation at the conversion of living epithelial cells to dead corneocytes, and consists of three major steps: formation of the intracellular keratin network, cornified envelopes and intercellular lipids. After cornification, the SC undergoes chemical reactions to form the mature SC with different functional layers. Finally, the SC is shed off at the surface ('desquamation'), mediated by a cascade of several proteases. This review will be helpful to understand our expanding knowledge of the biology of the SC, where immunity meets external antigens.
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