p63, a member of the p53 superfamily, is an essential cell fate determinant for stratified epithelium. Deficiency of p63 leads to lack of differentiated epithelium from the skin and the presence of trace undifferentiated cells left in the dermis. We found that transcriptionally active isoforms of p63, TAp63β and TAp63γ, activated the skin-specific promoter of bullous pemphigoid antigen 1 (BPAG-1). The p63-response element was localized between bases -177 and -153 upstream of exon 1 in the BPAG-1e promoter, whereas regions surrounding the response element suppressed transcriptional responses to p53 and TAp73β, resulting in p63-specific activation of the promoter. This represents a novel molecular mechanism by which target gene induction by p63 is distinguished from induction by other p53 family members.