Glypicans are heparan sulfate proteoglycans that are bound to the outer surface 
of the plasma membrane by a glycosyl-phosphatidylinositol anchor. Homologs of 
glypicans are found throughout the Eumetazoa. There are six family members in 
mammals (GPC1 to GPC6). Glypicans can be released from the cell surface by a 
lipase called Notum, and most of them are subjected to endoproteolytic cleavage 
by furin-like convertases. In vivo evidence published so far indicates that the 
main function of membrane-attached glypicans is to regulate the signaling of 
Wnts, Hedgehogs, fibroblast growth factors and bone morphogenetic proteins 
(BMPs). Depending on the context, glypicans may have a stimulatory or inhibitory 
activity on signaling. In the case of Wnt, it has been proposed that the 
stimulatory mechanism is based on the ability of glypicans to facilitate and/or 
stabilize the interaction of Wnts with their signaling receptors, the Frizzled 
proteins. On the other hand, GPC3 has recently been reported to inhibit Hedgehog 
protein signaling during development by competing with Patched, the Hedgehog 
receptor, for Hedgehog binding. Surprisingly, the regulatory activity of 
glypicans in the Wnt, Hedgehog and BMP signaling pathways is only partially 
dependent on the heparan sulfate chains.