Group I p21-activated kinases (PAKs) regulate cell survival, proliferation and motility, all factors that contribute to tumorigenesis. The tumor suppressor NF2 negatively regulates group I PAKs, and mutation or loss of NF2 leads to subsequent PAK activation. Using immunohistochemistry, PAK was found to be phosphorylated/activated in asbestos-induced malignant mesotheliomas from Nf2-deficient mice. Inhibition of group I PAKs in patient-derived mesothelioma cell lines was sufficient to inhibit tumor cell proliferation and viability via inactivation of the AKT and Raf-MAPK pathways, suggesting that PAKs represent novel targets for therapeutic intervention in NF2-deficient malignancies. For details, see article by Menges and colleagues on page 1178.