Hepatic clearance receptors

Hepatic clearance receptors are a collective group of specialized proteins expressed on liver sinusoidal endothelial cells (LSECs) and parenchymal cells (hepatocytes) that facilitate the removal of macromolecules, pathogens, and metabolic waste from systemic circulation (Sørensen et al., 2012, PubMed: 22733818). On LSECs, key receptors include Stabilin-1 (STAB1), Stabilin-2 (STAB2), and the Mannose receptor (CD206), which are responsible for clearing hyaluronan, collagen fragments, and various glycoproteins (Ganesan et al., 2011, PubMed: 21454511). Hepatocytes primarily utilize the Asialoglycoprotein receptor (ASGPR) and the Low-density lipoprotein receptor (LDLR) to internalize desialylated proteins and lipid particles, respectively (D'Souza & Devarajan, 2015, PubMed: 25830940). These receptors play a vital role in maintaining physiological homeostasis and protecting the body from systemic inflammation by sequestering potentially harmful substances. In modern pharmacology, these receptors—particularly ASGPR—are extensively exploited for targeted drug delivery using N-acetylgalactosamine (GalNAc) conjugation to deliver RNA interference (RNAi) therapeutics directly to the liver (Springer & Dowdy, 2018, PubMed: 29954478). However, the high efficiency of these clearance mechanisms can also pose a challenge by rapidly removing therapeutic proteins and nanoparticles before they reach their intended non-hepatic targets.

Other names

Liver scavenger receptorsHepatic uptake receptorsSinusoidal clearance systemLSEC clearance receptorsHepatocyte uptake transporters

Receptor-mediated endocytosis and lysosomal degradation of endogenous ligands or drug-conjugates.