Hypothesis: Galactosyl and N‐acetylgalactosaminyl homeostasis: A function for mammalian asialoglycoprotein receptors

Mammalian livers express endocytic cell surface receptors that specifically bind natural or synthetic molecules containing terminal galactosyl or N‐acetylgalactosaminyl sugars. One of these hepatocyte receptors is the asialogly‐coprotein receptor, which mediates the endocytosis and subsequent lysosomal degradation of these glyco‐molecules. Although the receptor was discovered almost 30 years ago, the physiological reason why mammals have this receptor is still unknown. At the cellular level, the basic molecular function of the receptor is to mediate the uptake and ultimate degradation of galactosyl/N‐acetylgalactosaminyl‐containing molecules (ligands). At the organism level, however, the physiological function is uncertain. The identity of the natural ligands and the reasons for this elaborate receptor system to remove these ligands are both unknown. This article proposes an explanation for the purpose of this asialoglycoprotein receptor and its role in regulating the dynamic flux of galactosyl/N‐acetylgalactosaminyl glycoconjugates in mammals.