The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) plays a crucial role in regulating the cell cycle and promoting anti-proliferative activities. It functions as both a sensor and an effector of multiple anti-proliferative signals, including those mediated by the tumor suppressor protein p53. p21 inhibits cell cycle progression by binding to and inhibiting the kinase activity of cyclin-dependent kinases (CDKs) CDK2 and CDK1. It also interferes with DNA replication and DNA repair processes by binding to proliferating cell nuclear antigen (PCNA). p21 has both tumor suppressor and oncogenic activities, depending on the cellular context. In cancer, p21 can act as a tumor suppressor by promoting cell cycle arrest and inducing senescence, or as an oncogene by promoting cell proliferation and oncogenicity under certain conditions. The regulation of p21 expression involves transcriptional and post-transcriptional mechanisms, including the actions of various transcription factors and ubiquitin ligase complexes. Understanding the complex network of p21 regulation and its biological functions is essential for developing targeted therapies against cancer.The cyclin-dependent kinase inhibitor p21 (also known as p21WAF1/Cip1) plays a crucial role in regulating the cell cycle and promoting anti-proliferative activities. It functions as both a sensor and an effector of multiple anti-proliferative signals, including those mediated by the tumor suppressor protein p53. p21 inhibits cell cycle progression by binding to and inhibiting the kinase activity of cyclin-dependent kinases (CDKs) CDK2 and CDK1. It also interferes with DNA replication and DNA repair processes by binding to proliferating cell nuclear antigen (PCNA). p21 has both tumor suppressor and oncogenic activities, depending on the cellular context. In cancer, p21 can act as a tumor suppressor by promoting cell cycle arrest and inducing senescence, or as an oncogene by promoting cell proliferation and oncogenicity under certain conditions. The regulation of p21 expression involves transcriptional and post-transcriptional mechanisms, including the actions of various transcription factors and ubiquitin ligase complexes. Understanding the complex network of p21 regulation and its biological functions is essential for developing targeted therapies against cancer.