The skin is divided into epidermis, dermis, and hypodermis, the skin's outermost, middle, and inner layers. The human epidermal layer regularly undergoes renewal, where old, dead cells are replaced by new cells. Epidermal stem cells or EpiSCs divide and differentiate to restore the lost cells. For the renewal process, some EpiSCs continuously self-renew. In contrast, few others differentiate into transit-amplifying cells, which later form prickle or spinous cells, followed by granular cells, and finally, dead keratinized squames, which are routinely shed off the skin.

Many factors should be controlled and regulated to sustain the renewal process. These include stem cell and transit-amplifying or TA cell division rate, the time a cell takes to leave the basal layer and differentiate, and finally, the removal of old and dead cells. As the cells begin to differentiate, they express different keratin molecules. The basal cells express keratin markers K5 and K14, spinous cells have K1 and K10, granular cells have profilaggrin and loricrin, while the keratinized cells express filaggrin. In case of wound or tissue damage, the epithelial keratinocytes migrate to the wound site and re-epithelialize the site.

The epidermal stem cells are attached to the basal layer through β1-integrins expressed by stem cells. Integrins connect the actin filaments of the basal cells with the extracellular matrix. In addition to attachment, the integrins also play a role in signaling pathways. Other signaling pathways include Wnt, Hedgehog, Notch, BMP, and EGF, which are required to renew and maintain epidermal cells. Mutation in any of these pathways might cause skin cancer.