Complement component C9 (C9)

Complement component C9 is a 71-kDa glycoprotein primarily synthesized in the liver and secreted into the bloodstream as a key effector of the innate immune system. It serves as the terminal and most abundant component of the membrane attack complex (MAC), a multi-protein pore that mediates the lytic function of the complement cascade. Upon activation of the terminal pathway, multiple C9 monomers (typically 12 to 18) undergo a conformational change and polymerize around the C5b-8 complex to form a stable transmembrane channel, which leads to the osmotic lysis of target cells, particularly Gram-negative bacteria. Dysregulation of C9 and the resulting MAC formation is a central driver of tissue damage in various autoimmune and inflammatory disorders, such as paroxysmal nocturnal hemoglobinuria (PNH), myasthenia gravis, and neuromyelitis optica. In these conditions, the MAC inappropriately targets host cell membranes, leading to cell death and chronic inflammation. While established therapies like eculizumab and ravulizumab target C5 to indirectly prevent MAC formation, newer therapeutic strategies are exploring direct C9 inhibition, bispecific antibodies, and gene therapies to more precisely modulate terminal complement activity and protect host tissues from lytic damage.

Other names

C9Complement C9Complement component 9

Inhibition of membrane attack complex (MAC) assembly by preventing C9 polymerization or blocking its recruitment to the C5b-8 complex; indirect inhibition via upstream C5 blockade.