Hyaluronic acid receptor for endocytosis (HARE)

The hyaluronic acid receptor for endocytosis (HARE, Stabilin-2/Stab2) is a type I membrane protein predominantly expressed in liver sinusoidal endothelial cells, spleen, and lymph nodes[1]. It functions as a scavenger receptor and mediates the endocytosis of multiple extracellular matrix-derived ligands, most notably hyaluronan (hyaluronic acid, HA), but also heparin, dermatan sulfate, acetylated low-density lipoprotein, apoptotic cells, and others[1][2]. HARE is unique in that it clears a broad spectrum of systemic ligands, playing a critical role in maintaining extracellular matrix homeostasis and potentially acting as a systemic tissue-stress sensor[2]. The receptor is available in at least two isoforms, the 175-kDa and approximately 300-kDa forms, both of which can function independently as endocytic receptors for HA[1]. Ligand binding and uptake occur via clathrin-coated pit-mediated endocytosis, and for select ligands, this process leads to intracellular signaling events, including activation of NF-κB and subsequent gene expression changes[2]. HARE’s broad specificity and biological roles suggest it may be involved in responses to tissue injury, inflammation, and disease states characterized by abnormal matrix turnover, but it has not yet been developed as a direct therapeutic target in clinical medicine[2].

Other names

Stabilin-2Stab2175-kDa HARE (isoform)~300-kDa HARE (isoform)

Endocytosis of ligands via clathrin-coated pits upon binding to HARE; Subsequent intracellular signaling (e.g., NF-κB activation, ERK1/2 phosphorylation) triggered by select ligands (hyaluronan, heparin, dermatan sulfate, AcLDL); No direct therapeutic modulation reported