H-ficolin is a serum lectin synthesized (as a ~34 kDa polypeptide) predominantly by the liver and lung tissues and is one of the soluble pattern recognition receptors of the innate immune system. It is structurally similar to L- and M- ficolins, but is different in its tissue expression and binding affinities to pathogenic ligands. Ficolins have an amino (N)-terminal cysteine-rich region, a middle stretch of a collagen-like sequence, and a fibrinogen-like domain in the carboxy (C)-terminus. Three identical polypeptides form a structural (triple helical) subunit, with the help of the collagen-like domain. Further oligomerization of this subunit results in different sized H-ficolin molecules in circulation. The polypeptides in the structural subunit are cross-linked by disulphide bonds in the N-terminal region and the fibrinogen-like domain forms a globular structure. Thus, the overall structure of H-ficolin also resembles mannose/mannan- binding lectin (MBL). The primary role of H-ficolin is that of a pattern recognition receptor, recognizing acetylated sugar residues on the cell surface of different bacteria, viruses and other pathogens. There are two pathways by which H-ficolin may participate in a host defense response: 1) It activates the complement lectin pathway, via MBL/ficolin associated serine proteases (MASPs), that converges with the classical complement pathway at the level of complement C4, and 2) it may also act directly as an opsonin, enhancing phagocytosis by binding to cell-surface receptors present on phagocytic cells.