asialoglycoprotein

Asialoglycoprotein refers to a glycoprotein that has been desialylated, meaning its terminal sialic acid residues have been removed to expose galactose or N-acetylgalactosamine residues. This desialylation can occur via sialidases in plasma or on cell surfaces, exposing galactose-containing termini that flag the glycoprotein for clearance.

The exposure of galactose residues targets asialoglycoproteins for rapid removal from circulation by the liver. This clearance is mediated primarily by the asialoglycoprotein receptor (ASGPR) on hepatocytes. ASGPR is a calcium-dependent C-type lectin receptor that binds terminal galactose and GalNAc with high affinity and mediates receptor-controlled endocytosis and lysosomal degradation of desialylated glycoproteins, thereby regulating plasma levels of these molecules and maintaining glycoprotein homeostasis.

ASGPR is expressed predominantly on hepatocytes and is composed of subunits encoded by ASGR1 and ASGR2, forming a receptor that facilitates uptake of ligands with terminal galactose residues. The pathway serves not only for normal protein turnover but also as a route for hepatic drug delivery; ligands such as galactose- or GalNAc-containing structures (notably triantennary GalNAc) are exploited to target the liver via ASGPR.

In clinical and research contexts, changes in desialylation or ASGPR function can influence glycoprotein half-lives. The term asialoglycoprotein thus describes the desialylated state of glycoproteins and their liver-directed clearance mechanism.