Integrin beta4 is a transmembrane protein expressed predominantly on epithelial cells. In human epidermis integrin beta4 associates with integrin beta6. Integrin alpha6beta4 is concentrated at the basement membrane zone, where it localizes to specialized adhesion structures called hemidesmosomes. In addition to its adhesive functions, keratinocyte integrin beta4 has been identified as an important regulator of epidermal homeostasis. This review summarizes the current knowledge regarding the role of integrin beta4 in keratinocyte adhesion, migration, as well as growth and differentiation. Changes in integrin beta4 expression in pathological conditions in skin and mucosa, especially those associated with human papillomavirus infection, are described.