TP53 encodes the p53 protein, a critical tumor suppressor and transcription factor that serves as the guardian of genome stability 1. The protein functions as a multifunctional transcription factor that directly regulates expression of approximately 500 genes involved in cell cycle arrest, DNA repair, senescence, autophagy, and apoptosis in response to cellular stress 2. Upon activation by stress stimuli, p53 governs an anti-proliferative transcriptional program that prevents tumorigenesis 1. TP53 mutations occur in approximately 50% of human cancers, making it the most frequently mutated gene in cancer 21. In myeloid neoplasms, TP53 mutations are found in 10-15% of cases and represent one of the most important prognostic factors, with multihit TP53 mutations associated with particularly poor outcomes 3. Most cancer-causing mutations are missense substitutions within the DNA-binding domain, with hotspot mutations at residues R175, Y220, G245, R248, R273, or R282 representing ~35% of all missense mutations 4. Germline TP53 mutations cause Li-Fraumeni syndrome, characterized by predisposition to multiple cancer types with significant clinical heterogeneity even within families carrying identical mutations 5. The protein's diverse roles extend beyond cancer to fertility, aging, longevity, and environmental adaptation 6.