Trp53 knockout mice and patients with germline TP53 mutations (Li-Fraumeni syndrome—LFS) (4,5) are highly cancer prone, whereas Trp63 deficiency is perinatally lethal (3,6) due to a lack of skin and other developmental defects that are shared by patients with a spectrum of syndromes associated with TP63 mutations (7). Here, TP63 is linked to Li-Fraumeni syndrome.