Epidermis is composed mainly of keratinocytes and is the ma-jor barrier of human body. The development and maintenance of normal epithelial structures and functions require the transcription factor p63. The p63 gene encodes proteins with structures similar to that of p53, including an N-terminal transactivation (TA) domain, a DNA-binding domain and a carboxy-oligomerization domain. TAp63 and ΔNp63 (p63 isoforms without TA domain) regulate a wide range of target genes that are important for embryonal development and epithelial integrity. Mutations of p63 gene cause epidermal abnormalities characterized by ectodermal dysplasia. Recent reports have indicated that p63 plays important role in tumorigenesis as well. However, the relative importance of TAp63 and ΔNp63 in epidermal development and tumorigenesis re-mains mostly unclear and awaits further investigation. In this review, we summarize the current knowledge on the structure and function of p63 and its isoforms.