Kallikreins

Kallikreins are a group of serine proteases with diverse physiological roles. In humans they are divided into plasma kallikrein and the tissue kallikreins, a family of kallikrein-related peptidases (KLK1–KLK15). The KLK genes are largely clustered on chromosome 19, while the plasma kallikrein gene KLKB1 encodes prekallikrein, the circulating precursor of plasma kallikrein.

Plasma kallikrein is activated from prekallikrein by factor XIIa and, once active, cleaves high-molecular-weight kininogen to release bradykinin. Bradykinin acts on B2 receptors to induce vasodilation and increased vascular permeability, contributing to inflammation and pain. The kallikrein-kinin system is regulated by inhibitors such as C1 esterase inhibitor and kallistatin; excessive bradykinin can cause angioedema in C1 inhibitor deficiency.

Tissue kallikreins are secreted serine proteases expressed in various tissues, including skin, kidney, and the male reproductive tract. They often process propeptides and extracellular substrates, participate in proteolytic cascades, and contribute to processes such as skin desquamation and semen liquefaction. Individual KLKs have tissue-specific roles; several (for example KLK3/PSA, KLK7, KLK5, KLK2, KLK14) are studied as biomarkers in cancer and other diseases.

Clinical and research relevance: Abnormal kallikrein activity is implicated in inflammatory and cardiovascular conditions, hereditary angioedema, and cancer. The KLK family remains a focus for diagnostic markers and therapeutic targets, with ongoing studies of enzymatic regulation and substrate specificity.