Heparan sulfate (HS) proteoglycans are expressed on cell surfaces and in the extracellular matrix, and take part in developmental, regenerative, as well as pathological processes. By interaction with extracellular matrix components, growth factors, enzymes, and their inhibitors, they regulate and influence tissue distribution of the cells and biological activities of the proteins. N-sulfated heparan sulfate proteoglycans are located in specific microdomains in the plasma membrane, independent on those formed around N-acetyl-rich heparan sulfate, and play different role in the cell signaling.