SERPING1 encodes C1 esterase inhibitor (C1-INH), a serine protease inhibitor that functions as the primary regulator of the classical complement pathway 1. C1-INH forms proteolytically inactive stoichiometric complexes with C1r and C1s proteases, controlling complement activation 2. Beyond complement regulation, C1-INH is the major controller of the kallikrein-kinin system and regulates blood coagulation and fibrinolysis 2. Deficiency or dysfunction of SERPING1-encoded C1-INH causes hereditary angioedema (HAE), an autosomal dominant disorder affecting approximately 1 in 50,000 people worldwide 1. SERPING1 mutations account for types I and II HAE: type I involves quantitative C1-INH deficiency (most common), while type II involves dysfunctional protein 2. Over 748 different SERPING1 variants have been documented, including de novo mutations occurring in ~15% of cases 3. C1-INH deficiency leads to uncontrolled kallikrein-kinin system activation, generating bradykinin and causing recurrent angioedema affecting subcutaneous tissues, gastrointestinal tract, and upper airways 2. Clinically, HAE typically presents in early adulthood with nonpitting edema triggered by stress, infection, or trauma 1. Current treatments include C1-INH concentrate infusions, kallikrein inhibitors, and bradykinin receptor antagonists for acute attacks, with long-term prophylaxis using similar agents 1. Emerging evidence suggests SERPING1 may also function as a tumor suppressor in lung adenocarcinoma 4.