In addition to the response to DNA damage and the maintenance of genome integrity which gained this protein the title of “The guardian of the genome” [11], p53 has been reported to have important roles also in the regulation of metabolism, ROS response, epigenetic modifications, epithelial–mesenchymal transition (EMT), and tumor microenvironment and inflammation (Figure 1) [8]. The gene discussed is TP53; the disease is neoplasm.