Human TMEM2 Is Not a Hyaluronidase but a Regulator of Hyaluronan Metabolism

The study "1393 Human TMEM2 is not a hyaluronidase but a regulator of hyaluronan metabolism" investigates the role of human TMEM2 (hTMEM2) in hyaluronan (HA) degradation. HA, a glycosaminoglycan abundant in skin, has different effects depending on its size: high molecular weight HA is anti-inflammatory and anti-angiogenic, while fragmented HA is pro-inflammatory and pro-angiogenic. The study found that while HYBID (another protein) is responsible for the first step of HA depolymerization, hTMEM2 does not function as a hyaluronidase (an enzyme that breaks down HA), contrary to its mouse counterpart mTMEM2. Instead, hTMEM2 appears to regulate HA metabolism, as its knockdown enhanced HA depolymerization. This was confirmed by transfecting HYBID and TMEM2 expression plasmids into HEK293T cells. The study also found that certain amino acid residues conserved in HA-degrading proteins are substituted in hTMEM2, which may explain its different function.