AKT is a central player in tumorigenesis, involved in regulating various cellular processes. The study by Mayo and Donner highlights AKT's role in regulating the Mdm2/p53 pathway. Early studies identified AKT's oncogenic potential through the cloning of the viral oncogene v-akt. AKT is a family of closely related, highly conserved proteins, including AKT1, AKT2, and AKT3, which are involved in cell survival, proliferation, and metabolism. AKT activation is a multistep process involving membrane translocation and phosphorylation, regulated by PI3K. AKT phosphorylates various substrates, including Mdm2 and p53, affecting cell cycle progression and apoptosis. AKT also regulates the activity of other proteins, such as glycogen synthase kinase 3, IκB kinase, and endothelial nitric oxide synthase, which are involved in angiogenesis and vascular tone. AKT activation can contribute to tumor invasion and metastasis by stimulating the secretion of matrix metalloproteinases. The study by Mayo and Donner shows that AKT phosphorylation is necessary for the nuclear translocation of Mdm2, which regulates p53 levels and activity. AKT also restrains the tumor suppressor p21 and p27, preventing cell cycle arrest. The involvement of AKT in diverse tumorigenic activities suggests that AKT activation alone may be sufficient to induce cancer. However, wild-type forms of Akt are only poorly transforming. The study highlights the central role of AKT in several processes considered hallmarks of cancer, including growth signal autonomy, tumor invasion, and metastasis. The expanding number of substrates implicated in tumorigenesis highlights the central role of AKT kinases in many human cancers. Therefore, there is growing interest in identifying inhibitors or modulators of the PI3K/AKT pathway for the development of novel therapeutic strategies.AKT is a central player in tumorigenesis, involved in regulating various cellular processes. The study by Mayo and Donner highlights AKT's role in regulating the Mdm2/p53 pathway. Early studies identified AKT's oncogenic potential through the cloning of the viral oncogene v-akt. AKT is a family of closely related, highly conserved proteins, including AKT1, AKT2, and AKT3, which are involved in cell survival, proliferation, and metabolism. AKT activation is a multistep process involving membrane translocation and phosphorylation, regulated by PI3K. AKT phosphorylates various substrates, including Mdm2 and p53, affecting cell cycle progression and apoptosis. AKT also regulates the activity of other proteins, such as glycogen synthase kinase 3, IκB kinase, and endothelial nitric oxide synthase, which are involved in angiogenesis and vascular tone. AKT activation can contribute to tumor invasion and metastasis by stimulating the secretion of matrix metalloproteinases. The study by Mayo and Donner shows that AKT phosphorylation is necessary for the nuclear translocation of Mdm2, which regulates p53 levels and activity. AKT also restrains the tumor suppressor p21 and p27, preventing cell cycle arrest. The involvement of AKT in diverse tumorigenic activities suggests that AKT activation alone may be sufficient to induce cancer. However, wild-type forms of Akt are only poorly transforming. The study highlights the central role of AKT in several processes considered hallmarks of cancer, including growth signal autonomy, tumor invasion, and metastasis. The expanding number of substrates implicated in tumorigenesis highlights the central role of AKT kinases in many human cancers. Therefore, there is growing interest in identifying inhibitors or modulators of the PI3K/AKT pathway for the development of novel therapeutic strategies.