The alimentary tract of earthworm secretes a group of proteases with a relative wide substrate specificity. In 1983, six isozymes were isolated from earthworm with fibrinolytic activities and called fibriniolytic enzymes. So far, more isozymes have been found from different earthworm species such as Lumbricus rubellus and Eisenia fetida. For convenience, the proteases are named on the basis of the earthworm species and the protein function, for instance, Eisenia fetida protease (EfP). The proteases have the abilities not only to hydrolyze fibrin and other protein, but also activate proenzymes such as plasminogen and prothrombin. In the light of recent studies, eight of the EfPs contain oligosaccharides chains which are thought to support the enzyme structure. Interestingly, EfP-II has a broader substrate specificity presenting alkaline trypsin, chymotrypsin and elastase activities, but EfP-III-1 has a stricter specificity. The protein crystal structures show the characteristics in their specificities. Earthworm proteases have been applied in several areas such as clinical treatment of clotting diseases, anti-tumor study, environmental protection and nutritional production. The current clinical utilizations and some potential new applications of the earthworm protease will be discussed in this paper. 1. Introduction Earthworm has been recorded with a long history. Five hundred years ago, Shizhen Li compiled the famous medical book Compendium of Material, in which the earthworm (Earth dragon) was recorded as a drug prescribed for antipyretic and diuretic purposes in the form of dried powder in clinic. Now the remedy is still used in the folk. In the end of 19th century, Frédéricq [1] discovered one enzyme secreted from the alimentary tract of earthworm. Then several proteases were separated from the earthworm in 1920 [2]. They could dissolve casein, gelatin, and albumin. This was the preliminary research about the earthworm proteases. Large-scale research about earthworm protease began in 1980. Mihara et al. [3] isolated a group of proteases with fibrinolytic activity from the earthworm Lumbricus rubellus. Subsequently different purification methods were applied to isolate the enzymes, including gel filtration, affinity chromatography, ion exchanging chromatography, and high-pressure liquid chromatography (HPLC). More proteases have been obtained from different species, such as lumbrokinase [4], earthworm-tissue plasminogen activator [5], earthworm plasminogen activator [6–11], component A of EFE (EFEa) [12, 13], and biologically active glycolipoprotein
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