Complement component C6 of 934 aas and 1 TMS; targets phagocytic and some non phagocytic cells (McCormack et al. 2013).  Expressed constitutively in phagocytes and inducibly in parenchymal tissue-forming cells. It is a transmembrane protein of cytosolic vesicles, derived from multiple organelles that translocate to and fuse with bacterium-containing vesicles. Subsequently, perforin-2 polymerizes and forms large clusters of 100 Å pores in the bacterial surface with perforin-2 cleavage products present in the bacteria. Perforin-2 is also required for the bactericidal activity of reactive oxygen and nitrogen species as well as hydrolytic enzymes (McCormack et al. 2015). Perforin-2 exists in membrane-bound (P2a) and secretory (P2b) isoforms, both present in human macrophages. P2a promotes fusion of vesicles with lysosomes, and may therefore play important roles in immune defense (Xiong et al. 2017). Loss of MPEG1 causes increased susceptibility to microbial infection. MPEG1 expression is upregulated in response to proinflammatory signals such as tumor necrosis factor alpha (TNFα) and lipopolysaccharides (LPS). Furthermore, germline mutations in MPEG1 have been identified in connection with recurrent pulmonary mycobacterial infections. Structural studies on MPEG1 revealed that it can form oligomeric pre-pores and pores. The unusual domain arrangement within the MPEG1 architecture suggests a novel mechanism of pore formation that may have evolved to guard against unwanted lysis of host cells (Bayly-Jones et al. 2020).