The plasma protease C1-inhibitor (C1-INH, SERPING1)) like all extracellular serine proteinase inhibitors (serpins) is secreted via the endoplasmic reticulum (ER)-Golgi pathway (Pan S et al. 2011). SERPING1 (C1-INH) is produced mainly in hepatocytes, reaching in healthy individuals a plasma concentration of 0.21–0.39 g/l (Prandini MH et al. 1986; Wouters D et al. 2008). SERPING1 can be produced and secreted from other cell types like peripheral blood monocytes, fibroblasts, and endothelial cells (Katz Y & Strunk RC 1989; Schmaier AH et al. 1989; Prada AE et al. 1998). SERPING1 is highly glycosylated plasma protein, bearing both N- and O-glycans (Stavenhagen K et al. 2018). SERPING1 belongs to the serine protease inhibitor (serpin) superfamily of structurally similar but functionally diverse proteins that use a conformational change to inhibit target enzymes (Silverman GA et al. 2001; Gettins PG 2002; Law RH et al. 2006). Serpins are globular proteins with a conserved structure of 7- 9 α-helices and 3 β-pleated sheets and a protruding reactive center loop (RCL) (Silverman GA et al. 2001; Gettins PG 2002; Law RH et al. 2006; Sanrattana W et al. 2019). In native serpins, the RCL, located outside the tertiary core of the serpin, forms a flexible stretch of approximately 20 amino acids, which provides structural flexibility in a solvent-exposed environment. They act on their target proteases by means of a suicide-substrate mechanism involving the cleavage of the RCL and its insertion into β-sheet A (Gettins PG 2002; Pan S et al. 2011; Khan MS et al. 2011). As a result, conformational changes take place in the serpins that ultimately trap and inactivate the targeted protease (Gettins PG 2002; Pan S et al. 2011; Khan MS et al. 2011; Sanrattana W et al. 2019). Serpins are conformationally labile and many of the disease-linked mutations of serpins result in misfolding or in formation of inactive, pathogenic polymers (Law RH et al. 2006). Under normal physiological conditions, SERPING1 (C1-INH) inhibits the activated forms of the serine proteases involved in the complement pathway (C1r and C1s), the contact system (FXIIa, FXIa, and kallikrein) as well as fibrinolytic proteases such as plasmin, tPA, and uPA (Sim et al. 1979; Arlaud et al. 1979; Kaplan AP & Ghebrehiwet B 2010).