HYAL

HYAL refers to a family of hyaluronidase enzymes encoded by HYAL genes in vertebrates. Hyaluronidases hydrolyze hyaluronic acid, a large glycosaminoglycan in the extracellular matrix, and thereby contribute to tissue remodeling, cell migration, and various physiological and pathological processes. In humans, the HYAL gene family includes several members with distinct expression patterns and substrate specificities.

In humans, the HYAL family comprises HYAL1, HYAL2, HYAL3, HYAL4, and SPAM1 (also known as HYAL5). HYAL1 is the major lysosomal hyaluronidase responsible for breaking down hyaluronan into small fragments, functioning optimally in acidic environments. HYAL2 is a cell-surface, GPI-anchored enzyme that cleaves high-molecular-weight hyaluronan into intermediate-sized fragments at the cell surface; these products can then be degraded by HYAL1 in the lysosome. HYAL3’s enzymatic activity in humans is not well defined and may be catalytically inactive or have a limited role. HYAL4 has activity more specific for chondroitin sulfate and dermatan sulfate rather than hyaluronan. SPAM1 (HYAL5) is a sperm-specific hyaluronidase implicated in fertilization by aiding penetration of the egg’s zona pellucida.

Clinical and research relevance: Altered HYAL expression or activity is associated with diseases involving extracellular matrix remodeling, such as cancer progression and inflammatory conditions. Hyaluronidases are also used clinically to enhance tissue permeability for drug delivery and in various research contexts to study hyaluronan turnover. Evolutionarily, HYAL genes show diversification across vertebrates, contributing to species- and tissue-specific hyaluronan metabolism.