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Keratins are the characteristic structural proteins of the highly cornified epidermis of the skin, feathers, and hoof. Keratin proteins provide the structural basis for the unique properties of the biomaterial horn and its protective function against a wide range of environmental factors. Hoof horn is produced through a complex process of differentiation (keratinization) of epidermal cells. Formation and biochemical binding of keratin proteins and synthesis and exocytosis of intercellular cementing substance (ICS) are the hallmarks of keratinization. It is finalized by the programmed death of the living epidermal cells, i.e., cornification, that turns the living epidermal cells into dead horn cells. The latter become connected by the intercellular cementing substance. The functional integrity of hoof horn essentially depends on a proper differentiation, i.e., keratinization of hoof epidermal cells. Keratinization of hoof epidermis is controlled and modulated by a variety of bioactive molecules and hormones. This process is dependent on an appropriate supply of nutrients, including vitamins, minerals, and trace elements. Regulation and control of differentiation and nutrient flow to the epidermal cells play a central role in determining the quality and, consequently, the functional integrity of hoof horn. Decreasing nutrient supply to keratinizing epidermal cells leads to horn production of inferior quality and increased susceptibility to chemical, physical, or microbial damage from the environment. A growing body of evidence suggests that hormones, vitamins, minerals, and trace elements play critical roles in the normal development of claw horn and correct keratin formation.