The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis. In addition to p53, mammalian cells contain two p53 family members, p63 and p73, which are similar to p53 in both structure and function. While p63 can induce p53-responsive genes and apoptosis, mutation of p63 rarely results in tumors. Research investigators frequently observe amplification of the p63 gene in squamous cell carcinomas of the lung, head and neck. The p63 gene contains an alternative transcription initiation site that yields a truncated ?Np63 lacking the transactivation domain, and alternative splicing at the carboxy-terminus yields the ?, ?, and ? isoforms.