Which structure do GPI-anchored proteins end up facing after their synthesis?

GPI-anchored proteins, or glycosylphosphatidylinositol-anchored proteins, are a specific class of membrane proteins that are tethered to the cell membrane by a lipid tail derived from a glycosylphosphatidylinositol molecule. During their synthesis in the endoplasmic reticulum, these proteins are directed towards the cell surface.

After their synthesis and subsequent modification, GPI-anchored proteins are transported through the secretory pathway, ultimately reaching the plasma membrane. The GPI anchor embeds the protein into the outer leaflet of the lipid bilayer, ensuring that the functional domains of the protein are positioned outside the cell, interfacing with the extracellular environment. This orientation facilitates various functions, including signaling and cell adhesion.

Consequently, after synthesis, GPI-anchored proteins are on the cell exterior surface, precisely where their biological roles take effect.