Hyaluronan (HA) Receptors: Discovery, Function & Pathology

Hyaluronan (HA) is typically a long polymer of the repeating disaccharide, glucuronic acid‐β‐(1‐3)‐N‐acetylglucosamine polymerized by β(1‐4) bonds, with no obvious active site for biological activity. However, this dynamic polymer is vital for life in all metazoans and has a diverse array of functional characteristics due to the proteins that bind with it. HA‐binding proteins (hyalectins) confer hyaluronan's biological activity in cells and tissues. A subset of HA‐binding proteins are receptors that attach hyaluronic acid polymers to cell surfaces or organelles. In this article, we will review the well‐known hyaluronan receptors (CD44, RHAMM, Stabilin‐2, etc.) as well as lesser‐known receptors (TLR2/4, Layilin, etc.) that are biologically linked to hyaluronan activity with respect to function, expression, and significance in homeostasis and disease.