Perforin, a Ca2+-dependent pore forming protein found in the granules of natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), was once proposed to be “the sole mediator of target cell destruction” (Ewen et al. 2012). However, in the late 1970s perforin was revealed to lack the protease activity required for apoptotic induction (Ewen et al. 2012). To identify other proteases that may be responsible, multiple researchers independently investigated the composition of CTL and NK cell granules (Boivin et al. 2009). Percoll density gradients were used to separate granules from NK cells and gel filtration then removed perforin, leaving an enriched pool of serine proteases. These “granule-associated enzymes” were subsequently named granzymes (Masson and Tschopp 1987). Cation exchange chromatography separated the granzymes into distinct clusters...
The authors wish to apologize to the many authors involved in studies that were uncited in this article and acknowledge that numerous references were not included due to space/reference limitation. Many of the references therefore refer to review articles where the original studies are cited.