PAK1, or p21-activated kinase 1, is a serine/threonine kinase known for its role as an effector of the small GTPases Rac1 and Cdc42. It is involved in a plethora of cellular functions, including cytoskeletal dynamics, cell cycle regulation, cell survival, and apoptosis. Research has highlighted the significance of PAK1 in aging and longevity. In the nematode Caenorhabditis elegans, PAK1 function limits lifespan under basal conditions by inhibiting the forkhead box transcription factor DAF-16. Interestingly, the depletion of PAK extends lifespan and ameliorates age-related phenotypes in a premature aging mouse model, suggesting that PAK is not only an oncogenic kinase but also an aging kinase. Moreover, PAK1 has been identified as a potential therapeutic target in cancer due to its involvement in multiple oncogenic signaling pathways. The kinase also plays a central role in major cell proliferation pathways, such as the Wnt/β-catenin and EGFR/HER2/MAPK pathways, and is involved in the regulation of apoptosis and NF-κB pathways, cell cycle progression, and autophagy.
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