Abstract The highly adaptive and sophisticated network of our immune system ensures a potent defense against a variety of possible threats. As a part of this machinery, cytotoxic T lymphocytes (CTLs), upon antigen recognition, are inducing programmed cell death by forming an immunological synapse (IS) between CTL and target cell, followed by release of granzyme B and perforin from lytic granules into the synaptic cleft. Whereas some mechanisms underlying the fusion of lytic granules with the plasma membrane have already been determined, temporal and spatial organization of these vesicles right before their fusion at the IS still remains elusive. From chemical synapses in the hippocampus it is known, that vesicle fusion occurs only at the active zone which is being formed by an exclusive number of CAZ (cytomatrix of the active zone) proteins like the 420 kDa protein bassoon. Our qRT-PCR data from primary human and murine CTLs show that CAZ proteins are not only expressed, but are specifically upregulated in activated CTLs, suggesting a possible role during the killing process for example as scaffolding proteins. As specific target killing is a process of paramount importance for survival, it seems likely that vesicle fusion at the IS is precisely organized as well. We present data from primary CTLs derived from CAZ-deficient mice that investigate a possible contribution of CAZ proteins in the organisation and function of the IS.