HYALs

HYALs refers to a family of hyaluronidases, enzymes that catalyze the hydrolysis of hyaluronic acid (HA), a large polysaccharide component of the extracellular matrix and cell surfaces. In vertebrates, HYALs belong to glycoside hydrolase family 56 and include several paralogs with distinct tissue distributions and subcellular localizations.

In humans, the HYAL gene family includes HYAL1, HYAL2, HYAL3, HYAL4, and the sperm-specific SPAM1 (also called PH-20). HYAL2 is commonly attached to the cell surface via a GPI anchor and initiates extracellular HA degradation, producing intermediate-sized fragments. HYAL1 is a lysosomal enzyme that further degrades HA fragments into smaller oligosaccharides within the lysosome. HYAL3 has limited or uncertain catalytic activity in humans, and HYAL4 is reported to have specificity for chondroitin sulfate and may have reduced activity on HA. SPAM1 is a sperm-derived hyaluronidase essential for fertilization, helping penetrate the cumulus oophorus.

Biological roles of HYALs include turnover of the extracellular matrix, enabling tissue remodeling during development, wound healing, and inflammation. Abnormal HYAL expression or activity has been linked to pathological processes such as cancer progression, where HA fragmentation can influence cell motility, and to infertility in the context of SPAM1 function.

Researchers study HYALs as potential therapeutic targets, and various inhibitors and modulators are used to investigate HA metabolism in health and disease.