enzymes play a key role in determining the synthesis of the various types of glycans. The order of action of the enzymes is reflected in their position in the Golgi stack: In archaea and prokaryotes Similar N-glycan biosynthesis pathway have been found in prokaryotes and Archaea. However, compared to eukaryotes, the final glycan structure in eubacteria and archaea does not seem to differ much from the initial precursor made in the endoplasmic reticulum. In eukaryotes, the original precursor oligosaccharide is extensively modified en route to the cell surface. Function N-linked glycans have intrinsic and extrinsic functions. Within the immune system, the N-linked glycans on an immune cell's surface will help dictate that migration pattern of the cell, e.g. immune cells that migrate to the skin have specific glycosylations that favor homing to that site. The glycosylation patterns on the various immunoglobulins including IgE, IgM, IgD, IgA, and IgG bestow them with unique effector functions by altering their affinities for Fc and other immune receptors. Glycans may also be involved in "self" and "non self" discrimination, which may be relevant to the pathophysiology of various autoimmune diseases. In some cases, interaction between the N-glycan and the protein stabilizes the protein through complex electronic effects. Clinical significance Changes in N-linked glycosylation has been associated with different diseases including rheumatoid arthritis, type 1 diabetes, Crohn's disease, and cancers. Mutations in eighteen genes involved in N-linked glycosylation result in a variety of diseases, most of which involve the nervous system. Importance in therapeutic proteins Many therapeutic proteins in the market are antibodies, which are N-linked glycoproteins. For example, Etanercept, Infliximab and Rituximab are N-glycosylated therapeutic proteins. The importance of N-linked glycosylation is becoming increasingly evident in the field of pharmaceuticals. Although bacterial or yeast protein production systems have significant potential advantages such as high yield and low cost, problems arise when the protein of interest is a glycoprotein. Most prokaryotic expression systems such as E. coli cannot carry out post-translational modifications. On the other hand, eukaryotic expression hosts such as yeast and animal cells, have different glycosylation patterns. The proteins produced in these expression hosts are often not identical to human protein and thus, cause immunogenic reactions in patients. For example, S.cerevisiae (yeast) often produce high-mannose glycans which are immunogenic. Non-human mammalian expression systems such as CHO or NS0 cells have the machinery required to add complex, human-type glycans. However, glycans produced in these