Cytotoxic T lymphocytes (CTLs) are immune cells of the lymphoid cell lineage that survey and recognize infected or malignant antigen presenting cell. Upon encountering the target, CTLs release the contents of their cytotoxic secretory vesicles into the synaptic cleft. The internal components of these vesicles include the pore forming protein perforin, the pro-apoptotic serine proteases granzymes, as well as the luminal proteoglycan serglycin. Serglycin is a highly o-glycosylated intracellular proteoglycan, mainly expressed in endothelial and immune cell types, where its main function is thought to be the storage and/or delivery of soluble proteins to secretory vesicles. Previously, serglycin was shown to play an important role in the cytotoxic capacity of CTLs, including its involvement in the storage of perforin and granzyme B. However, the exact mechanism and the structural basis of this multimolecular interaction remains elusive. In this project, we investigate the role of various structural and putative functional motifs present in serglycin, with the aim of elucidating its interaction with perforin and granzymes. These studies will determine the critical role of serglycin in the cytotoxic activity of CTLs.