Biosynthesis of glycosylphosphatidylinositol-anchored proteins in the ER has been extensively studied, whereas the molecular events during the transport of GPI-APs from the ER to the cell surface are poorly understood. PGAP2 encoded a Golgi/ER-resident membrane protein. The low surface expression of GPI-APs was due to their secretion into the culture medium. GPI-APs were modified/cleaved by two reaction steps in the mutant cells. First, the GPI anchor was converted to lyso-GPI before exiting the trans-Golgi network. Second, lyso-GPI-APs were cleaved by a phospholipase D after transport to the plasma membrane.PGAP2 deficiency caused transport to the cell surface of lyso-GPI-APs that were sensitive to a phospholipase D. PGAP2 is involved in the processing of GPI-APs required for their stable expression at the cell surface.