Kallikrein
Kallikreins are a subgroup of serine proteases, enzymes capable of cleaving peptide bonds in proteins. In humans, plasma kallikrein ("KLKB1") has no known paralogue, while tissue kallikrein-related peptidases ("KLKs") encode a family of fifteen closely related serine proteases. These genes are localised to chromosome 19q13, forming the largest contiguous cluster of proteases within the human genome. Kallikreins are responsible for the coordination of various physiological functions including blood pressure, semen liquefaction and skin desquamation. Occurrence. In 1934, Eugen Werle reported finding a substance in the pancreas of humans and various animals in such large amounts that the pancreas  could be taken for its site of origin. He named it kallikrein, by derivation from the Greek word for pancreas. Since then, similar enzymes have been found in the biological fluids of humans and other mammals, as well as in some snake venoms. Venom. The caterpillar known as "Lagoa crispata" contains poison glands attached to hypodermic spines, which produce and inject venom that has been characterized as kallikrein in nature. The venom of solenodons and some shrews like the northern short-tailed shrew consist of multiple, independently-evolved paralogous kallikrein 1 ("KLK1") serine proteases, which cause hypotensive effects "in vivo . Plasma kallikrein. The KLKB1" gene encoding plasma kallikrein is located on chromosome 4q34-35. It is synthesised as an inactive precursor, prekallikrein, which must undergo proteolytic processing to become activated. This is facilitated by factor XII, PRCP or other stimuli. Plasma kallikrein liberates kinins (bradykinin and kallidin) from the kininogens, peptides responsible for the regulation of blood pressure and activation of inflammation. It is also capable of generating plasmin from plasminogen: Structure. Kallikrein is homologous to factor XI and consists of four apple domains and one serine protease domain. Tissue kallikreins. Distinct from plasma kallikrein, tissue kallikreins (KLKs) are expressed  throughout the human body and perform various physiological roles. As some kallikreins are able to catalyse the activation of other kallikreins, several cascades involving these proteases have been implicated in the regulation of homeostatic functions. Function. Similar to KLKB1, three tissue kallikreins KLK1, KLK2 and KLK12 also participate in regulation of blood pressure via the activation of bradykinin. KLK2, KLK3, KLK4, KLK5 and KLK14 are expressed in the prostate and are thought to be responsible for regulating semen liquefaction through hydrolysis of semenogelin. Desquamation of the skin is likely controlled by KLK5, KLK7 and KLK14, which are expressed in the  outermost layer of the epidermis and cleave cellular adhesion proteins. Additionally, KLK6 and KLK8 are associated with neuronal plasticity in the central nervous system. Genes. There are 15 known human tissue kallikreins: KLK1, KLK2, KLK3, KLK4, KLK5, KLK6, KLK7, KLK8, KLK9, KLK10, KLK11, KLK12, KLK13, KLK14, KLK15 Clinical significance. Kallikrein-related peptidases are targets of active investigation by drug researchers as possible biomarkers for cancer. Prostate-specific antigen (PSA; hk3, human kallikrein gene 3) and human glandular kallikrein (hK2) are used as tumor markers for prostate cancer. Ecallantide, lanadelumab, and berotralstat are FDA-approved drugs that inhibit kallikrein and can  be used for managing Hereditary Angioedema.