Archetypal members of the family are complement C9 and perforin, both of which function in human immunity. C9 functions by punching holes in the membranes of Gram-negative bacteria. Perforin is released by cytotoxic T cells and lyses virally infected and transformed cells. In addition, perforin permits delivery of cytotoxic proteases called granzymes that cause cell death. Deficiency of either protein can result in human disease. Structural studies reveal that MACPF domains are related to cholesterol-dependent cytolysins (CDCs), a family of pore forming toxins previously thought to only exist in bacteria.