Mannan-binding lectin-associated serine protease (MASP)

Mannan-binding lectin-associated serine proteases (MASPs) are a family of enzymes—primarily MASP-1, MASP-2, and MASP-3—that play a critical role in the activation of the complement system, a key component of innate immunity [1, 17]. MASP-2 is the primary effector of the lectin pathway, where it cleaves complement components C4 and C2 to initiate the cascade upon recognition of pathogens or damaged host cells [4, 11]. MASP-1 acts as an essential activator of MASP-2 and also contributes to the coagulation cascade, while MASP-3 is the primary activator of pro-factor D, making it a vital regulator of the alternative complement pathway [13, 15, 17]. Dysregulation or overactivation of these proteases is implicated in various inflammatory and thrombotic disorders, including IgA nephropathy, hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), and paroxysmal nocturnal hemoglobinuria (PNH) [1, 3, 7, 8]. Therapeutic strategies targeting MASPs, such as the monoclonal antibodies narsoplimab (targeting MASP-2) and zaltenibart (targeting MASP-3), aim to selectively inhibit specific complement pathways to reduce tissue damage and inflammation while preserving other immune functions [1, 3, 4, 6]. These targets are particularly attractive because their inhibition can block pathological complement activation without broadly suppressing the entire immune system [1, 3, 9].

Other names

MASP-1MASP-2MASP-3Mannose-binding protein-associated serine proteasePRSS5CRARFRaRFMAP-1MAp44MAp19

Selective inhibition of MASP-2 blocks the lectin pathway of complement activation by preventing the cleavage of C4 and C2 [4, 11]. Inhibition of MASP-3 prevents the conversion of pro-factor D to active factor D, thereby blocking the alternative pathway [3, 17].