Mannan-binding lectin-associated serine protease 1 (MASP-1)

Mannan-binding lectin-associated serine protease 1 (MASP-1) is a multifunctional serine protease that serves as the primary initiator of the lectin pathway of the complement system, a vital arm of innate immunity [1, 11]. Encoded by the MASP1 gene, it is synthesized as a zymogen and autoactivates upon the binding of pattern recognition molecules, such as mannan-binding lectin (MBL) or ficolins, to pathogen surfaces [1, 9]. Once active, MASP-1 is the exclusive activator of MASP-2, which then propagates the complement cascade by cleaving C4 and C2 [37]. Beyond its immunological role, MASP-1 exhibits thrombin-like activity, contributing to the coagulation cascade by cleaving fibrinogen and factor XIII, and it promotes inflammation by releasing bradykinin from high-molecular-weight kininogen [4, 17]. In clinical contexts, MASP-1 is implicated in a variety of conditions, including 3MC syndrome (caused by genetic mutations), sepsis, cardiovascular diseases, and various cancers where its serum levels serve as a prognostic biomarker [1, 5, 12, 21]. It also plays a non-canonical role in embryogenesis, specifically in directing neural crest cell migration [4, 5]. While MASP-1 is a compelling therapeutic target for complement-mediated and inflammatory disorders, specific inhibitors like SGMI-1 are currently limited to preclinical research [22, 39]. However, natural inhibitors such as C1-inhibitor, which is used clinically for hereditary angioedema, are known to effectively modulate MASP-1 activity [10, 33].

Other names

MASP13MC1CRARFCRARF1MAP1MASPMASP3MAp44PRSS5RaRFMannose-binding lectin-associated serine protease 1Mannan-binding lectin serine protease 1Complement-activating component of Ra-reactive factor

Serine protease inhibition, Lectin pathway inhibition, Prevention of MASP-2 activation, Reduction of pro-inflammatory and pro-coagulant signaling [7, 24, 37]