Gas6 (Growth Arrest Specific 6) is a secreted 75 kDa multimodular protein that is up-regulated by a wide variety of cell types in response to growth arrest. It is expressed by endothelial cells, fibroblasts, neurons, smooth muscle cells, and platelets, and it plays a role in vascular, thrombotic, atherosclerotic, inflammatory, autoimmune, renal, and cancer pathologies (1, 2). Both Gas6 and the related Protein S contain an extensively gamma -carboxylated N-terminal Gla domain, four EGF-like repeats, and two C-terminal Laminin G-like domains. And like Protein S, Gas6 is dependent upon vitamin K for activity. Within the Gla, EGF-like, and Laminin G-like domains, mouse Gas6 shares 83%, 94%, and 41% aa sequence identity with the equivalent regions in human Gas6, rat Gas6, and mouse Protein S, respectively. Gas6 binds to and induces signaling through the receptor tyrosine kinase TAM subfamily, which includes Axl, Dtk/Tyro3, and Mer (3). Shed soluble forms of Axl and Mer retain the ability to bind Gas6 and function as decoy receptors (4, 5). Gas6 participates in tissue homeostasis by protecting cells from stress-induced apoptosis and promoting apoptotic cell phagocytosis. The affinity of the gamma -carboxylated Gla domain for phosphatidylserine contributes to the role of Gas6 in phagocytosis as well as the cellular entry of select viruses (6, 7). Gas6 can function as a pro-inflammatory molecule by promoting platelet activation (8, 9) and can also inhibit inflammatory cytokine production from monocytes, macrophages, and microglia (10). In addition, Gas6 induces the proliferation of cardiac fibroblasts, Schwann cells, vascular smooth muscle cells, and the differentiation of NK cell precursors (11-14). It also inhibits VEGF-induced angiogenesis (15) and can have either positive or negative effects on tumor cell proliferation and invasion (16, 17).