Proline-rich tyrosine kinase-2 (PYK2; EC 2.7.10.2) is related to focal adhesion kinase (FAK; EC 2.7.10.2) and shares a similar domain structure (FERM, kinase, proline-rich and FAT domains) as well as common phosphorylation sites. Both kinases act as critical mediators for the activation of signaling pathways that regulate cell migration, proliferation, and survival. By coordinating adhesion and cytoskeletal dynamics with survival and growth signaling, FAK and Pyk2 represent molecular therapeutic targets in cancer cells as malignant cells often exhibit defects in these processes. Despite their structural similarity, PYK2 and FAK display a number of significant differences (distribution, activation). Although PYK2 can be activated following integrin mediated adhesion, PYK2 is primarily activated in response to a variety of stimuli that increase intracellular calcium. Upregulation of PYK2 expression has been noted in several human tumors, gliomas, and with advancing WHO grade, and define it a potential target for disease modulation, particularly as it pertains to invasive cancers, osteoporosis, and inflammatory cellular responses[1].