The AP. The AP begins with activation of C3 and leads to the assembly of the membrane attack complex as a mechanism of protection from infectious agents. Dysregulation of this pathway in disease is most often by the loss of function of regulatory proteins and can lead to endothelial injury, platelet activation, and thrombosis. Regulatory genes (−) that have been shown to be mutated in aHUS are shown in gold. CFH, CFI, MCP, and THBD cooperate to regulate complement activation or inactivate endothelial cell surface-bound C3b, protecting endothelial cells from complement-mediated injury. C3 mutations affect the ability of C3 to bind to regulatory proteins and CFB mutations are gain-of-function mutations (+) that result in an increased stability of the C3 convertase.