Plasma and tissue kallikrein (KLKB1/KLK1)

Plasma and tissue kallikreins are distinct serine proteases that serve as key components of the kallikrein-kinin system (KKS), a proteolytic cascade essential for regulating inflammation, vascular permeability, and blood pressure [1.1.1, 1.3.1]. Plasma kallikrein (encoded by KLKB1) is primarily synthesized in the liver and circulates in the blood, where it is activated by factor XIIa to release bradykinin from high-molecular-weight kininogen (HMWK) [1.1.3, 1.2.1]. Tissue kallikrein (primarily KLK1) is expressed in various tissues, such as the kidneys and pancreas, and releases kallidin from low-molecular-weight kininogen (LMWK) [1.1.3, 1.5.4]. Dysregulation of the plasma kallikrein pathway is the hallmark of hereditary angioedema (HAE), a condition characterized by recurrent, severe swelling due to excessive bradykinin production [1.2.2, 1.4.2]. Consequently, plasma kallikrein has become a major therapeutic target, with several approved inhibitors like lanadelumab and berotralstat used for HAE prophylaxis [1.2.1, 1.2.3]. While tissue kallikreins are also involved in cardiovascular and inflammatory processes, they represent a broader family of 15 peptidases (KLKs) with diverse roles, including the use of KLK3 (PSA) as a cancer biomarker [1.1.1, 1.5.4].

Other names

KLKB1KLK1Plasma kallikreinTissue kallikreinFletcher factorKininogeninKallikrein-kinin system

Inhibition of serine protease activity to prevent the cleavage of kininogens and the subsequent release of vasoactive kinins, specifically bradykinin and kallidin.