Mannose-binding lectin-associated serine protease (MASP) (MASP)

Mannose-binding lectin-associated serine proteases (MASPs) are essential enzymatic components of the lectin pathway of the complement system, a key arm of the innate immune response. The family consists of three main proteases—MASP-1, MASP-2, and MASP-3—which circulate in plasma as complexes with pattern recognition molecules such as mannose-binding lectin (MBL) and ficolins (UniProt O00187, P48740). Upon recognition of specific carbohydrate patterns on pathogens or damaged host cells, MASP-2 is activated and cleaves complement components C4 and C2 to generate C3 convertase, while MASP-1 and MASP-3 provide essential amplification and cross-talk with the alternative pathway (PubMed: 30108568). Pathological overactivation of these enzymes is implicated in a variety of complement-mediated diseases, including IgA nephropathy, hematopoietic stem cell transplant-associated thrombotic microangiopathy (HSCT-TMA), and age-related macular degeneration (PubMed: 31551140). Therapeutic strategies targeting MASPs, particularly MASP-2, aim to selectively inhibit the lectin pathway while leaving the classical pathway intact to preserve some immune function. Clinical-stage inhibitors like narsoplimab have demonstrated potential in reducing inflammation and tissue injury in patients with rare complement-driven disorders (Omeros Corporation, 2024).

Other names

MBL-associated serine proteaseMannan-binding lectin-associated serine proteaseMASP-1MASP-2MASP-3MASP1MASP2MASP3PRSS5

Inhibition of the lectin pathway of the complement system by blocking the proteolytic activity of MASP enzymes, thereby preventing the cleavage of complement components C4 and C2 (for MASP-2) or C2 and factor B (for MASP-1/3).