The article discusses the cytoplasmic functions of the tumor suppressor protein p53, which is known for its nuclear transcriptional activities but also exhibits cytoplasmic activities that contribute to its tumor suppressive role. p53 can trigger apoptosis and inhibit autophagy in the cytoplasm, independent of its transcriptional activity. In the mitochondria, p53 induces mitochondrial outer membrane permeabilization (MOMP), leading to the release of pro-apoptotic factors and cell death. The mechanisms by which p53 triggers MOMP involve interactions with Bcl-2 family proteins, particularly Bax and Bak. Additionally, p53 inhibits autophagy, a process crucial for cellular adaptation to stress, by regulating the AMP-dependent kinase (AMPK) and mammalian target of rapamycin (mTOR). The dual role of p53 in inhibiting autophagy and inducing MOMP may be a coordinated response to facilitate cell death. The article also explores the regulation of p53's nuclear and cytoplasmic functions through post-translational modifications and protein interactions, and discusses the implications of p53 mutations in cancer and aging.The article discusses the cytoplasmic functions of the tumor suppressor protein p53, which is known for its nuclear transcriptional activities but also exhibits cytoplasmic activities that contribute to its tumor suppressive role. p53 can trigger apoptosis and inhibit autophagy in the cytoplasm, independent of its transcriptional activity. In the mitochondria, p53 induces mitochondrial outer membrane permeabilization (MOMP), leading to the release of pro-apoptotic factors and cell death. The mechanisms by which p53 triggers MOMP involve interactions with Bcl-2 family proteins, particularly Bax and Bak. Additionally, p53 inhibits autophagy, a process crucial for cellular adaptation to stress, by regulating the AMP-dependent kinase (AMPK) and mammalian target of rapamycin (mTOR). The dual role of p53 in inhibiting autophagy and inducing MOMP may be a coordinated response to facilitate cell death. The article also explores the regulation of p53's nuclear and cytoplasmic functions through post-translational modifications and protein interactions, and discusses the implications of p53 mutations in cancer and aging.