Glypican-1 (GPC1), glypican-2 (GPC2) and glypican-3 (GPC3) are members of the glypican family of heparan sulfate proteoglycans, which attach to the cell membrane via a glycosylphosphatidylinositol (GPI) anchor. Cell-surface heparan sulfate proteoglycans participate in molecular events that regulate cell adhesion, migration, and proliferation. Glypican-2, a cell surface proteoglycan bearing heparan sulfate, may have a function related to the motile behaviors of developing neurons. Ligation of cell-surface glypican-2 with midkine (MK) or an; against epitope-tagged glypican-2 induces cell adhesion and promotes neurite outgrowth. MK binds to heparan sulfate chains of glypican-2 in a manner similar to syndecan-3, but different localization of epitope-tagged glypican-2 and syndecan-3 on the surface of N2?cells suggests that they may play different roles in MK-mediated neural function.