[3] Glypicans seem to play a vital role in developmental morphogenesis, and have been suggested as regulators for the Wnt [4][5][6]and Hedgehog cell signaling pathways.

They have additionally been suggested as regulators for fibroblast growth factor and bone morphogenic protein signaling.

[3] For all members of the glypican family, the C-terminus of the protein is attached to the cell membrane covalently via a glycosylphosphatidylinositol (GPI) anchor.

Within 50 amino acids of this GPI anchor, the heparan sulfate chains attach to the protein core.

Therefore, unlike syndecans the heparan sulfate glycosaminoglycan chains attached to glypicans are located rather close to the cell-membrane.

[3] Glypicans are critically involved in developmental morphogenesis, and have been implicated as regulators in several cell signaling pathways.

One commonly proposed mechanism suggests that glypicans behave as co-receptors which bind both the ligand and the receptor.

[5] A cysteine-rich domain at the N-lobe of GPC3 has been identified to form a Wnt-binding hydrophobic groove including phenylalanine-41 that interacts with Wnt.

[8] Drosophila Dally mutants have irregular wing, antenna, genitalia, and brain development.

While the phenotype associated with this condition can vary from mild to lethal, common symptoms include macroglossia, cleft palate, syndactyly, polydactyly, cystic and dysplastic kidneys, congenital heart defects, and a distinct facial appearance.

Researchers currently speculate that GPC3 is a negative regulator of cell proliferation, and this would explain why patients with SGBS experience overgrowth.

Furthermore, oftentimes GPC3 expression occurs during embryonic development in these tissues, and is subsequently re-expressed during tumor progression.

GPC3 is an oncofetal protein in both liver and intestine, as GPC3 is typically only expressed during embryonic development but also found in cancerous tumors.

GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis.

[9] Immunotoxins and chimeric antigen receptor (CAR) T cells targeting GPC2 have been developed for treating neuroblastoma and other GPC2-positive cancers.

[16] Glypicans can modify cell signaling pathways and contribute to cellular proliferation and tissue growth.

[17] Extracellular localization of the other glypican in Drosophila, dally-like, is also required for the proper level of Hedgehog signaling in the developing wing.