The mannan-binding lectin (MBL) pathway of the complement system is initiated by the binding of MBL or ficolin to specific carbohydrate structures found on the surface of a variety of microorganisms. This binding is followed by the activation of MBL-associated serine proteases (MASPs). There are four known MASPs: MASP-1, MASP-2, MASP-3 and Map19 (also known as sMAP, a small, separately synthesized fragment of MASP-2). MASPs are secreted as single chain precursors and are processed into a heavy chain (A) and catalytic light chain (B) linked by disulfide bonds. All MASPs form homo-dimers and individually associate with MBL and the ficolins in a Ca2+-dependent manner. MASP-3 is an alternatively spliced product from the MASP-1 gene, containing an identical A chain, but an entirely different B chain. MASP-3 is an approximately 100 kDa protein and associates with both MBL and L-ficolin in the presence of Ca2+. The MASP3 dimer can be disrupted by EDTA. MASP-3 is expressed mainly but not exclusively in the liver. Liver expressed MASP-3 is secreted into the blood. Unlike MASP-2, no proteolytic activity on complement proteinss C2, C3 and C4 for MASP-3 has been detected. MASP-3 exerts inhibitory activity on MASP-2 function. However, no natural substrates for MASP-3 are known. MASP-3 concentration in healthy human serum is normally distributed with a mean value of 3796 ng/ml. MASP-3 is present at birth at approximately 80% of the level measured 6, 9 and 12 months after birth. The MASP-3 level is stable throughout a 1-year period. The high expression of MASP-3 in astrocytes indicates that MASP-3 might also be involved in other functions that could be important in the brain. In multiple sclerosis patients, high MASP-3 levels seem to have a positive effect (median MASP-3 levels: 4539 ng/ml). MASP-3 deficiencies are currently not reported.