Glycosylphosphatidylinositol-glycan (GPI) is an anchor to specific cell surface proteins known as GPI-anchored proteins (APs) that are localized in lipid rafts and may act as cell co-receptors, enzymes and adhesion molecules. The present review investigated the significance of GPI biosynthesis class phosphatidylinositol-glycan (PIG)M and PIGX in GPI synthesis and their implications in human health conditions.