{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSERPING1 encodes the C1 inhibitor (C1‐INH), a key serine protease inhibitor that maintains the balance of several proteolytic cascades. C1‐INH is essential for the regulation of the classical and lectin complement pathways by inactivating proteases such as C1r, C1s, and MASP‐1/2, as well as for controlling the contact system that drives bradykinin formation. Structural studies have revealed that its proper function is critically dependent on a highly glycosylated serpin domain, disulfide‐bond formation, and a unique N‐terminal region that helps maintain its metastable conformation and modulates interactions with cofactors such as heparin. In addition, C1‐INH binds to cell adhesion molecules via oligosaccharide determinants, which may further contribute to the control of leukocyte–endothelial interactions and overall inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "12"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in SERPING1 underlie the autosomal dominant disorder hereditary angioedema (HAE), and numerous studies have documented extensive allelic heterogeneity and diverse molecular mechanisms associated with disease. Disease‐causing variants include missense, nonsense, frameshift, splicing defects, and large rearrangements that result in either quantitative or qualitative deficiencies of C1‐INH. Some mutations even exert dominant‐negative effects by promoting intracellular misfolding and aggregation, thereby reducing the secretion of the wild‐type protein. These studies, based on comprehensive genetic screening in multiple populations, highlight the diverse nature of SERPING1 mutations that not only serve as the primary cause of HAE but also correlate variably with clinical severity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its classical role in complement inhibition and prevention of angioedema, C1‐INH plays additional roles in immune modulation and host defense. It can interfere directly with leukocyte adhesion through its glycan structures and may be sequestered by certain pathogens (for example, Bordetella pertussis) as a mechanism of immune evasion. Emerging evidence also suggests that altered C1‐INH levels or function can impact conditions as diverse as age‐related macular degeneration and even influence neural tissue architecture, underscoring a broader role in inflammatory and degenerative processes. 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