p53 dubbed “guardian of the genome”, is a protein (and transcription factor) discovered in 1979 and represents one of the most studied proteins (there are 84,538 abstracts in PubMed mentioning this protein). It has received such massive attention due to its biological role as a tumor suppressor. Thus, insights into p53 can be translated into knowledge of tumors. Mak et al. hypothesized that p53 has an important role in the protection of the heart, due to the observation that apoptosis of cardiomyocytes in end-stage human heart failure, correlates with elevated p53 levels. The authors created transgenic mice without the p53 gene. Gene expression in cardiac tissues were measured with microarrays. Mice without the p53 gene developed hypertropy of the heart. p53 was found to regulate mitochondrial biogenesis as well as energy metabolism. Limitations of the study include a somewhat outdated technique for measuring gene expression as well as the focus on perturbing a single component. We could also not easily find the sample size. Nevertheless, the study implicates p53 as an important component in a protein network in the heart.