thumb|A simpler drawing of a GPI anchor, missing two EtNP bridges on the intermediate mannose groups.
Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide variety of biological processes. GPI is composed of a phosphatidylinositol group linked through a carbohydrate-containing linker (glucosamine and mannose glycosidically bound to the inositol residue) and via an ethanolamine phosphate (EtNP) bridge to the C-terminal amino acid of a mature protein. The two fatty acids within the hydrophobic phosphatidyl-inositol group anchor the protein to the cell membrane.
Synthesis
Glycosylated (GPI-anchored) proteins contain a signal sequence, thus directing them to the endoplasmic reticulum (ER). The protein is co-translationally inserted in the ER membrane via a translocon and is attached to the ER membrane by its hydrophobic C terminus; the majority of the protein extends into the ER lumen. The hydrophobic C-terminal sequence is then cleaved off and replaced by the GPI-anchor. As the protein processes through the secretory pathway, it is transferred via vesicles to the Golgi apparatus and finally to the plasma membrane where it remains attached to a leaflet of the cell membrane. Since the glypiation is the sole means of attachment of such proteins to the membrane, cleavage of the group by phospholipases will result in controlled release of the protein from the membrane. The latter mechanism is used in vitro; i.e. membrane proteins released from membranes in enzymatic assays are glypiated proteins.
The inositol residue is modified with palmitate or myristate at position 2 prior to mannose and ethanolamine phosphate transfer. This is most often removed soon after addition to the C terminus of a protein in the endoplasmic reticulum; in nucleated cells, only 5 to 10 percent of mature GPI-anchored proteins retain the marker, however, in erythrocytes, the majority of GPI-anchored proteins are acylated with myristate on the anchor. In Trypanosoma brucei, by contrast, mannosyltransferase activity does not require acylation of the inositol residue and consequently unacylated GPI anchors are transferred to the parasite's variant surface glycoprotein.
Without these proteins linked to the cell surface, the complement system can lyse the cell, and high numbers of RBCs are destroyed, leading to hemoglobinuria.
For patients with HPMRS, disease-causing mutations have been reported in the genes PIGV, PIGO, PGAP2 and PGAP3.
In other species
The variable surface glycoproteins from the sleeping sickness protozoan Trypanosoma brucei are attached to the plasma membrane via a GPI anchor.