p63 protein is a type II integral membrane protein that is predominantly localised in rough endoplasmic reticulum. Its gene is a member of the p53 gene family and encodes for at least six major isotypes with transactivating, death-inducing activities (TAp63) and dominant-negative activities (deltaNp63). p63 protein is detected in a variety of human, including proliferating cells of epithelium, cervix, urothelium and prostate. p63 protein is also expressed in most poorly differentiated squamous cell carcinomas. In epithelial tissues, the dominant isotype, deltaNp63, lacks an acidic N-terminus corresponding to the transactivating domain of p53. The delta N-isotype is also abundantly expressed in nasopharyngeal carcinomas. p63 protein is required for prostate development and, in mice, it is essential for limb and epidermal morphogenesis. The human p63 gene is mutated in children with the disease Ectrodactyly, Ectodermal Dysplasia and Facial Clefts syndrome. In contrast to the p53 gene, the p63 gene is rarely mutated in human cancer. p63 protein is not detected in prostate adenocarcinoma but altered expression is a frequent event in bladder carcinogenesis and may contribute to the progression of bladder cancers.