glypican

Glypicans are a family of cell-surface heparan sulfate proteoglycans that attach to the outer leaflet of the plasma membrane via a glycosylphosphatidylinositol (GPI) anchor. Each glypican consists of a core protein of approximately 60–70 kDa to which one or more heparan sulfate chains are covalently linked. In humans there are six known members, GPC1 through GPC6, encoded by GPC1–GPC6 genes and expressed in a tissue-specific manner.

Glypicans regulate signaling by presenting or sequestering ligands such as Wnt, Hedgehog, fibroblast growth factors and bone morphogenetic proteins, acting as co-receptors or modulators. The outcome is context-dependent, promoting or inhibiting signaling depending on receptor composition and the extracellular environment. They can also influence cell growth, migration, and morphogenesis.

Glypicans play important roles in development and organogenesis; mouse knockouts show neural patterning and skeletal defects. In humans, defects in GPC3 cause Simpson-Golabi-Behmel syndrome, an X-linked overgrowth disorder. Dysregulation of glypicans is implicated in cancer; GPC3 is commonly upregulated in hepatocellular carcinoma and is investigated as a diagnostic marker and therapeutic target. Other family members, such as GPC2 and GPC5, are studied as targets in pediatric cancers.

Glypicans are GPI-anchored to the cell surface and can be released by phospholipase C–mediated cleavage of the GPI anchor, generating soluble ectodomains that continue to bind ligands. The heparan sulfate chains mediate interactions with growth factors and extracellular matrix components, shaping signaling in the local microenvironment.