Schematic representation of a currently accepted model for cell-mediated HA degradation. Catabolism of HA starts at the cell surface. CD44 binds HA extracellularly and facilitates its degradation by HYAL2. The degradation products (now in the range of 20-kDa polymers) are internalized into endosomes and then transported into the lysosomes where they get further degraded by HYAL1 into tetrasaccharides. N-acetyl glucosaminidase and glucuronidase enzymes then further degrade HA into monosaccharides. “Reprinted with permission, Cleveland Clinic Center for Medical Art & Photography © 2015. All Rights Reserved”.