Glycosylation of asparagine residues in Asn-X-Ser/Thr motifs in proteins commonly occur in the lumen of the endoplasmic reticulum (ER). Glucosidase I catalyzes the first step in the N-linked oligosaccharide processing pathway. It specifically removes the distal alpha 1,2-linked glucose residue from the Glc3-Man9-GlcNAc2 oligosaccharide precursor. Glucosidase I contains a short cytosolic tail, a single pass transmembrane domain and a large C-terminal catalytic domain located on the luminal side of the ER. Mutations in the gene encoding Glucosidase I result in the congenital disorder glycosylation (CDG-IIb), which is characterized by generalized hypotonia, dysmorphic features, hepatomegaly, hypoventilation, feeding problems, seizures and death. Two point mutations in the Glucosidase I gene have been identified and result in amino acid substitutions, namely Arg486Thr and Phe652Leu, that affect polypeptide folding and active site formation.