HYAL2

Hyaluronidase 2 (HYAL2), also termed lysosomal hyaluronidase, is a glycosylphosphatidylinositol (GPI)-anchored enzyme encoded by the HYAL2 gene. It hydrolyzes high-molecular-weight hyaluronan (HA) into intermediate fragments within acidic environments, often cooperating with HYAL1 for complete HA degradation. HYAL2 participates in HA catabolism, extracellular matrix remodeling, and cell signaling through interactions with HA receptors like CD44 and RHAMM. Its activity is implicated in the TGF-β/Smad pathway and angiogenesis regulation. Dysregulation of HYAL2 is associated with tumor progression, fibrosis, and metabolic disorders, particularly in cancers where HA degradation promotes invasion and metastasis. Current research explores HYAL2 as a therapeutic target; inhibitors such as modified HA derivatives and monoclonal antibodies are under preclinical investigation for oncology and fibrotic diseases. Recent studies also highlight its role in viral entry mechanisms, expanding potential therapeutic applications.