HYAL1 (hyaluronidase 1) is a primary enzyme responsible for degrading hyaluronic acid (HA), a major extracellular matrix component, with humans constituting approximately 5 grams of HA per day in a 70 kg adult 1. HYAL1 functions through catalytic breakdown of high molecular weight HA into smaller fragments, with activity regulated by multiple signaling pathways and transcriptional factors 2. Estrogen receptor α negatively regulates HYAL1 expression in breast cancer cells through binding to consensus estrogen response elements in the HYAL1 promoter 3. In disease contexts, HYAL1 expression promotes tumor progression and metastasis. WNT5B upregulates HYAL1 in osteosarcoma, driving cancer stem cell expansion, chemoresistance, and metastasis to lungs and liver by inhibiting the glycosaminoglycan hyaluronic acid 4. Similarly, HYAL1 elevation in colorectal carcinoma correlates with increased cell migration and invasiveness 5. HYAL1 overexpression appears in a succinylation-based prognostic model for colorectal cancer, where high-risk patients demonstrate significantly shorter overall survival 6. In aging, increased HYAL1 expression combined with decreased hyaluronan synthase (HAS3) reduces ovarian hyaluronan content, contributing to age-associated tissue stiffness and potential oocyte quality decline 7. HYAL1 deficiency causes mucopolysaccharidosis 9 1. Therapeutically, HYAL1 inhibitors including chicoric acid and testosterone propionate show potential for targeting pathophysiological processes 8.