In this review, we discuss recent advances in the molecular and structural basis of activation and regulation of the complement pathways followed by the discussion of one complement-mediated disease – atypical hemolytic uremic syndrome (aHUS) to illustrate how the knowledge of the structure–function relationships between complement proteins helps to understand aHUS physiopathology and aid in the development of targeted therapy. The gene discussed is VTN; the disease is atypical hemolytic-uremic syndrome.