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The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function\u2010altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating \u2018hyperinflammatory complement phenotypes\u2019. To treat these \u2018complementopathies\u2019, a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. 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