The epidermal layer of the skin provides an essential function as a protective barrier against insults from the external environment. The predominant cell type in the epidermis is keratinocytes and they are present in the stratified squamous epithelia. Progenitors of keratinocytes reside and divide in the basal layer of the epidermis. They then differentiate, migrate towards the surface of epidermis, and eventually withdraw from the cell cycle permanently. Keratinocyte proliferation, differentiation, and programmed cell death are complex and carefully choreographed processes. Apart from their protective functions, Human Epidermal keratinocytes express adhesion molecules and cytokines, further suggesting an implication in skin innate immunity, tissue homeostasis, wound healing, cancer development, and skin-based gene-therapy.