Mannan-binding lectin-associated serine protease 1, 2, and 3 (MASP-1/2/3)

Mannan-binding lectin-associated serine proteases (MASP-1, MASP-2, and MASP-3) are essential enzymatic components of the lectin pathway of the complement system (UniProt P48740, O00187). MASP-1 and MASP-2 work in tandem to initiate the complement cascade; MASP-1 serves as the primary activator that triggers MASP-2, which then cleaves C4 and C2 to generate C3 convertase (PubMed: 22110657). MASP-3, though sharing a gene with MASP-1, is uniquely responsible for the activation of factor D, thereby serving as a critical link to the alternative complement pathway (PubMed: 31551353). Pathological overactivation of these proteases is a driver in diseases such as IgA nephropathy, atypical hemolytic uremic syndrome (aHUS), and various thrombotic microangiopathies (PubMed: 33061124). Therapeutic strategies targeting MASP-2, such as the monoclonal antibody narsoplimab, are designed to block the lectin pathway and reduce inflammatory tissue damage (Omeros Corporation). Similarly, MASP-3 inhibitors like OMS906 are being investigated for their ability to modulate the alternative pathway in conditions like paroxysmal nocturnal hemoglobinuria (PNH). These targets are of high interest because inhibiting the lectin or alternative pathways can provide therapeutic benefits while leaving the classical complement pathway intact for fighting infections.

Other names

MBL-associated serine proteaseMannose-binding lectin-associated serine proteaseMASPPRSS27CRARF

Inhibition of the lectin and alternative pathways of the complement system by blocking the proteolytic activity of MASP enzymes, thereby preventing the formation of C3 convertase and subsequent inflammatory cascades (PubMed: 31551353, Omeros Corporation).