Abstract
Hyaluronan (HA) is one of the most abundant components of extracellular matrices. HA is a huge polysaccharide - a single linear HA polymer often exceeds 25,000 disaccharide units in length (~10(7) Da) and occupies the volume of a 300 nm diameter sphere. These unique biochemical and biophysical properties are accompanied by extremely rapid turnover of HA, which emphasizes the importance of not only its biosynthesis but also degradation in regulating the homeostasis and biological functions of HA. Further supporting the specific importance of HA degradation, a large body of evidence demonstrates that biological functions of HA are dependent on its size and degree of fragmentation. While considerable research has revealed the roles of the HYAL family hyaluronidases in HA catabolism and biology, the discovery of TMEM2 as a functional cell surface hyaluronidase, coupled with increasing data demonstrating its remarkable biological functions, have added a new dimension of research to the field of HA biology.