The transmembrane protein TMEM2 is a major cell-surface hyaluronidase that degrades HMW HA into low-molecular weight (LMW) ~5 kDa fragments.4–6 Notably, TMEM2’s cleavage activity is specific to non-sulfated HA and does not cleave other sulfated GAGs.4 Besides degradation caused by pathogen-derived external hyaluronidases, accelerated degradation of HA is found in other pathologic conditions including rheumatoid arthritis, diabetes, cancer, and inflammation,3,7 possibly caused by altered cellular HA metabolism. The gene discussed is CEMIP2; the disease is rheumatoid arthritis.