Syndecans are transmembrane heparan sulfate proteoglycans involved in the 
regulation of cell growth, differentiation, adhesion, neuronal development, and 
lipid metabolism. Syndecans are expressed in a tissue-specific manner to 
facilitate diverse cellular processes. As receptors and co-receptors, syndecans 
provide promising therapeutic targets that bind to a variety of physiologically 
important ligands. Negatively charged glycosaminoglycan chains of syndecans, 
located in the extracellular compartment, are critical for such binding. 
Functions of syndecans are as diverse as their ligands. For example, hepatic 
syndecan-1 mediates clearance of triglyceride-rich lipoproteins. Syndecan-2 
promotes localization of Alzheimer's amyloid Aβ peptide to the cell surface, 
which is proposed to contribute to amyloid plaque formation. Syndecan-3 helps 
co-localize the appetite-regulating melanocortin-4 receptor with its agonist, 
leading to an increased appetite. Finally, syndecan-4 initiates the capture of 
modified low-density lipoproteins by macrophages and thereby promotes the 
atheroma formation. We hypothesize that syndecan modifications such as 
desulfation of glycosaminoglycan chains may contribute to a wide range of 
diseases, from atherosclerosis to type 2 diabetes. At the same time, desulfated 
syndecans may have beneficial effects, as they can inhibit amyloid plaque 
formation or decrease the appetite. Despite considerable progress in 
understanding diverse functions of syndecans, the complex physiological roles of 
this intriguing family of proteoglycans are far from clear. Additional studies 
of syndecans may potentially help develop novel therapeutic approaches and 
diagnostic tools to alleviate complex human diseases such as cardiovascular and 
Alzheimer's diseases.