The article reviews the mechanisms by which mutant p53 proteins exert their cellular effects, focusing on the emerging mutant p53 transcriptome and the biological and clinical consequences of gain-of-function mutations. It highlights that while wild-type p53 is a tumor suppressor, mutant p53 can acquire novel activities that alter tumor cell behavior through interactions with other cellular proteins and regulation of transcriptional programs. The review discusses the discovery of p53 as a proto-oncogene, the establishment of its tumor suppressor role, and the gain-of-function hypothesis, which suggests that certain mutant p53 proteins have a positive role in tumorigenesis. It also explores the interaction between mutant p53 and cellular proteins, such as p63 and p73, and the regulation of transcription by mutant p53. The article emphasizes the importance of understanding the diverse activities of mutant p53 proteins and their implications for cancer biology and clinical outcomes.The article reviews the mechanisms by which mutant p53 proteins exert their cellular effects, focusing on the emerging mutant p53 transcriptome and the biological and clinical consequences of gain-of-function mutations. It highlights that while wild-type p53 is a tumor suppressor, mutant p53 can acquire novel activities that alter tumor cell behavior through interactions with other cellular proteins and regulation of transcriptional programs. The review discusses the discovery of p53 as a proto-oncogene, the establishment of its tumor suppressor role, and the gain-of-function hypothesis, which suggests that certain mutant p53 proteins have a positive role in tumorigenesis. It also explores the interaction between mutant p53 and cellular proteins, such as p63 and p73, and the regulation of transcription by mutant p53. The article emphasizes the importance of understanding the diverse activities of mutant p53 proteins and their implications for cancer biology and clinical outcomes.