I. Abstract Glycosylphosphatidylinositol (GPI) anchoring of cell surface proteins is the most metabolically expensive posttranslational lipid modification known, involving proteins that act through at least 11 sequential steps in the endoplasmic reticulum (ER). This chapter will focus on the first step in the biosynthesis of GPI anchors, the glycosylation of phosphatidylinositol (PI) to generate N‐acetylglucosamine (GlcNAc)‐PI. As the first committed step of the pathway, one might expect it to be subject to stringent regulation. Therefore, an important aspect of this chapter will be the growing evidence for various mechanisms that are employed to regulate GPI‐anchor production at the earliest stage.
