Gash, a ligand of receptor tyrosine kinases Axl, Sky, and Mer, potentiates cell prolifera tion and prevents cell death. It also contains ƒÁ-carboxylglutamic acid residues that mediate the interaction of some blood coagulation factors with negatively charged phos pholipids. In our previous study, we demonstrated that Gas6 specifically binds to phos phatidylserine(PS) and links Axl-expressing cells to the PS-coated surface. In this study, to further understand the biological role of the interaction of Gas6 with PS, we exam ined the effect of Gas6 on the uptake of PS liposomes by macrophages. In vitro phagocy tosis studies showed that Gas6 enhanced the uptake of PS liposomes approximately threefold and that the interaction of Gas6 with the surface of macrophages was essen tial for this enhancement. Analyses of the mechanism of the uptake of PS liposome sug gested that Gas6 interacts with PS liposome via its N-terminal Gla domain and with macrophages via its C-terminal domain. Like that of PS liposomes, the uptake of apop totic cells by macrophages was also enhanced, approximately twofold, in the presence of Gas6. These findings suggest that Gas6 may help phagocytic cells recognize cells with PS exposed on their surfaces, which is considered to be one of the mechanisms for clearing away dying cells. Thus, Gas6 may play a critical role in homeostasis by facilitating the clearance of PS-expressing cells.