The article provides a comprehensive overview of the discovery and research progress of p53 over the past 30 years. Initially, p53 was identified as a cellular partner of the SV40 Large Tumor Antigen, a viral oncoprotein. Over time, it was recognized that p53 is not an oncogene but a tumor suppressor frequently mutated in human cancers. The function of p53, a transcription factor induced by stress, was uncovered, leading to cell cycle arrest, apoptosis, and senescence. New functions, such as regulation of metabolic pathways and cytokines required for embryo implantation, were also discovered. The article highlights the evolution of p53 research, including the realization that p53 is a tumor suppressor rather than an oncogene, and the identification of the MDM2-MDM4 (HDM2) complex as the key regulator of p53 activity. The article also discusses the potential of p53-based therapies, including gene therapy and compounds that restore p53 activity, and the future directions of p53 research, such as the roles of p53 isoforms and modifications in various biological processes.The article provides a comprehensive overview of the discovery and research progress of p53 over the past 30 years. Initially, p53 was identified as a cellular partner of the SV40 Large Tumor Antigen, a viral oncoprotein. Over time, it was recognized that p53 is not an oncogene but a tumor suppressor frequently mutated in human cancers. The function of p53, a transcription factor induced by stress, was uncovered, leading to cell cycle arrest, apoptosis, and senescence. New functions, such as regulation of metabolic pathways and cytokines required for embryo implantation, were also discovered. The article highlights the evolution of p53 research, including the realization that p53 is a tumor suppressor rather than an oncogene, and the identification of the MDM2-MDM4 (HDM2) complex as the key regulator of p53 activity. The article also discusses the potential of p53-based therapies, including gene therapy and compounds that restore p53 activity, and the future directions of p53 research, such as the roles of p53 isoforms and modifications in various biological processes.