Hyaluronidases are a family of enzymes that catalyse the degradation of hyaluronic acid (HA). Karl Meyer classified these enzymes in 1971, into three distinct groups, a scheme based on the enzyme reaction products. The three main types of hyaluronidases are two classes of eukaryotic endoglycosidase hydrolases and a prokaryotic lyase-type of glycosidase. In humans, there are five functional hyaluronidases: HYAL1, HYAL2, HYAL3, HYAL4 and HYAL5 (also known as SPAM1 or PH-20); plus a pseudogene, HYAL6 (also known as HYALP1). The genes for HYAL1-3 are clustered in chromosome 3, while HYAL4-6 are clustered in chromosome 7. HYAL1 and HYAL2 are the major hyaluronidases in most tissues. GPI-anchored HYAL2 is responsible for cleaving high-molecular weight HA, which is mostly bound to the CD44 receptor. The resulting HA fragments of variable size are then further hydrolized by HYAL1 after being internalized into endo-lysosomes; this generates HA oligosaccharides. According to their enzymatic mechanism, hyaluronidases are hyaluronoglucosidases (), i.e. they cleave the (1->4)-linkages between N-acetylglucosamine and glucuronate. The term hyaluronidase may also refer to hyaluronoglucuronidases (), which cleave (1->3)-linkages. In addition, bacterial hyaluronate lyases () may also be referred to as hyaluronidases, although this is uncommon. Use as a drug Medical uses By catalyzing the hydrolysis of hyaluronan, a constituent of the extracellular matrix (ECM), hyaluronidase lowers the viscosity of hyaluronan, thereby increasing tissue permeability. It is, therefore, used in medicine in conjunction with other drugs to speed their dispersion and delivery. Common applications are ophthalmic surgery, in combination with local anesthetics. It also increases the absorption rate of parenteral fluids given by hypodermoclysis, and is an adjunct in subcutaneous urography for improving resorption of radiopaque agents. Hyaluronidase is also used for extravasation of hyperosmolar solutions. Besides, hyaluronidase is a recommended antidote for vinca alkaloid overdose or extravasation. Hyaluronidase can be injected to dissolve hyaluronic acid type dermal fillers and is the best treatment option for those looking at dissolving lip filler or dealing with related complications. Patrick Treacy is recognised to be among the first doctors worldwide to use hyaluronidase during vascular occlusion caused by these type of dermal fillers and to establish protocols for its use. Purified and recombinant hyaluronidases Four different purified hyaluronidases have been approved for use in the United States, three of animal origin and one recombinant. They are indicated as adjuvants in subcutaneous fluid administration for achieving hydration, for increasing the dispersion and absorption of other injected drugs, or