The asialoglycoprotein-receptor (ASGP-R) located on liver parenchymal cells was originally identified and characterized on the basis of its ability to bind glycoproteins bearing terminal galactose (Gal) or N-acetylgalactosamine (GalNAc); however, endogenous ligands for the ASGP-R have not to date been definitively identified. We have determined that the rat ASGP-R specifically binds oligosaccharides terminating with the sequence Sia␣2,6GalNAc␤1,4GlcNAc␤1,2Man. Bovine serum albumin chemically

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... ified with 10 -15 tetrasaccharides with the sequence Sia␣2,6GalNAc␤1,4GlcNAc␤1,2Man is cleared from the blood of the rat with a half-life of <1 min by a receptor located in the liver. We have isolated the receptor and identified it as the ASGP-R. Furthermore, we have determined that subunit 1 of the ASGP-R accounts for the binding of terminal Sia␣2,6GalNAc␤. Based on the newly defined specificity of the rat ASGP-R we hypothesize that glycoproteins bearing structures that are selectively modified with terminal Sia␣2, 6GalNAc␤ and are released into the blood may be endogenous ligands for the rat ASGP-R.