The half-life of protein-therapeutics in circulation can be dramatically altered by changing the glycosylation state, due to increased clearance by the kidney or hepatic receptors (Varki et al. (2003) “Essentials of Glycobiology”, 2nd edition, Cold Spring Harbor Lab. Press). For example, removal of all sialic acid residues from erythropoietin (EPO) to form asialoerythropoietin decreases its circulation half-life by more than 150-fold (Erbayraktar et al. (2003) Proc. Nat. Acad. Sci. 100, 6741).  

Glycosylation can also confer resistance to protease-cleavage-inactivation of proteins. Fibroblast growth factor 23 (FGF-23) is implicated in familial tumoral calcinosis (FTC), a metabolic disorder. One of the causes of FTC is lack of O-glycosylation of FGF-23, which renders it susceptible to cleavage and unable to be secreted (Kato et al. (2006) J. Biol. Chem. 281, 18370). Low-density lipoprotein receptor is protected from cleavage by O-glycosylation in the extracellular stalk region, and lack of glycosylation results in the loss of the receptor region (Kingsley et al. (1986) J. Biol. Chem. 102, 1576).  

Glycosylation of lipids is also important for a wide variety of purposes.  The glycosphingolipid gangliosides act as intracellular signaling molecules, and glycosylphosphatidylinositol can act as membrane attachments for proteins (GPI anchor).