GPISynthasen

GPISynthasen are a family of enzymes that catalyze the assembly of glycosylphosphatidylinositol (GPI) anchors, the glycolipid moiety that covalently attaches certain proteins to the cell membrane. These enzymes operate within the endoplasmic reticulum (ER) and sequentially add sugars and phosphate groups to a phosphatidylinositol backbone, forming a complex lipid structure that serves as a universal signal for protein attachment.

The GPI anchor biosynthetic pathway includes several distinct synthases, many of which are encoded by PIG (phosphatidylinositol glycan class) genes. Key enzymes are PIG-M, which initiates the process by adding N‑acetylglucosamine to phosphatidylinositol; PIG-P, which transfers phosphatidylinositol to the growing glycan; and PIG-B, which adds a second N‑acetylglucosamine residue. Subsequent enzymes add lactose, mannosyl and glucosyl residues, culminating in the release of the completed GPI anchor ready for transfer to the C‑terminus of a target protein.

Defects in GPISynthasen genes lead to inherited GPI deficient disorders (IGD). These conditions are characterized by intellectual disability, seizures, and developmental delay, underscoring the importance of proper GPI anchor synthesis for neuronal function. Diagnostic screening often involves measuring the surface expression of GPI‑anchored proteins such as CD59 or CD55 on lymphocytes.

GPISynthasen are highly conserved across eukaryotes, reflecting the fundamental role of GPI anchors in cell adhesion, signal transduction, and immune regulation. Research continues to clarify the structural biology of these enzymes and to develop therapeutic strategies for GPI deficiencies.