The antimicrobial protein granulysin (GNLY) is secreted from activated human cytotoxic T lymphocytes (CTL) and natural killer (NK) cells (Pena SV et al. 1997; Stenger S et al. 1998; Hanson DA et al. 1999; Ogawa K et al. 2003). The cationic GNLY binds to negatively charged surfaces found in bacteria causing defects in membranes of extracellular and intracellular pathogs (Stenger S et al. 1998; Ernst WA et al. 2000; Barman H et al. 2006). While showing strong antimicrobial activity, GNLY does not permeabilize cell membranes with eukaryotic lipid composition (Barman H et al. 2006). GNLY bound to lipid rafts or phospholipid on eukaryotic cell membranes can be internalized by lipid rafts and delivered to the early sorting endosomes which afterwards fuse with bacteria-containing phagosomes, where the GNLY-mediated lysis of bacteria is induced (Walch M et al. 2005, 2007). GNLY may require perforin as a cofactor to enter the host cells (Stenger S et al. 1998) However, it was also suggested that perforin promotes GNLY-mediated bacteriolysis not by the formation of stable pores that allow passive diffusion of GNLS but rather by an increase in endosome-phagosomes fusion triggered by an intracellular Ca(2+) rise (Walch M et al. 2007).