PRAK is a 471 amino acid protein with 20–30% sequence identity to the known MAP kinase-regulated protein kinases RSK1/2/3, MNK1/2 and MAPKAPK2/3. The p38 mitogen-activated protein kinase (MAPK) pathway plays an important role in cellular responses to inflammatory stimuli and environmental stress. There are at least six protein kinases that can be regulated by p38α and/or p38β. These downstream kinases of p38s include MAPK-activated protein kinase 2 (MAPKAPK2 or MK2), MAPKAPK3, MAPKinteracting kinase 1 (MNK1), MNK2, p38– activated/regulated protein kinase (PRAK or MAPKAPK5), and mitogen- and stress-activated protein kinase (MSK). PRAK can be activated in response to cellular stress and proinflammatory cytokines. T182 within the activation loop of PRAK has been determined to be the regulatory phosphorylation site. PRAK has been reoprted to be essential for ras-induced senescence and tumor suppression. PRAK mediates senescence upon activation by p38 in response to oncogenic ras.