HYAL3 encodes hyaluronidase 3, an enzyme that catalyzes hyaluronic acid degradation through hyaluronan catabolic processes 1. In reproductive physiology, HYAL3 facilitates sperm penetration into cumulus cells surrounding the egg and induces acrosome reactions [UniProt]. The enzyme regulates ovarian follicle development by inducing granulosa cell apoptosis through caspase-8/3 and PARP activation, contributing to follicular atresia [UniProt]. Notably, HYAL3 exhibits tissue-specific enzymatic activity, lacking hyaluronidase function in embryonic fibroblasts and granulosa cells in vitro [UniProt]. Clinically, HYAL3 has emerged as a potential disease biomarker. Genetic polymorphisms in HYAL3 are associated with primary open-angle glaucoma through hyaluronan metabolism disruption 2. In bladder cancer, elevated HYAL3 expression predicts poor overall survival and correlates with immune cell infiltration 3. HYAL3 mutations occur in ~10% of lung squamous cell carcinomas and associate with lymph node metastasis 4. Following acoustic trauma, HYAL3 expression changes contribute to cochlear inflammation via TLR4 signaling activation 5. In pancreatic cancer, HYAL3 is expressed in tumors alongside HYAL1 and HYAL2, supporting tumor-promoting hyaluronan degradation 6. These findings suggest HYAL3 serves dual roles in normal reproductive physiology and pathological tissue remodeling associated with cancer progression and inflammatory diseases.