Protein export from the endoplasmic reticulum (ER) is an essential process in all eukaryotes driven by the cytosolic coat complex COPII, which forms vesicles at ER exit sites for transport of correctly assembled secretory cargo to the Golgi apparatus. The COPII machinery must adapt to the existing wide variety of different types of cargo proteins and to different cellular needs for cargo secretion. The study of the ER export of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs), a special glycolipid-linked class of cell surface proteins, is contributing to address these key issues. Due to their special biophysical properties, GPI-APs use a specialized COPII machinery to be exported from the ER and their processing and maturation has been recently shown to actively regulate COPII function. In this review, we discuss the regulatory mechanisms by which GPI-APs are assembled and selectively exported from the ER.