Apoptosis, or programmed cell death, is essential for cellular regulation while its dysregulation is implicated in various diseases, including neurodegenerative disorders and cancer. Caspases, a family of cysteine-aspartic proteases, play a central role in apoptosis. Caspase-8, an initiator caspase, begins this pathway by responding to external pro-apoptotic signals. Once active, caspase-8 cleaves thus activates executioner caspases (-3, -6 and -7) which drive apoptotic processes. Despite research efforts to better understand the caspase-mediated apoptotic pathway, specific protein-protein interactions, specifically between initiator and executioner caspases, remain unknown. In this study, I aim to explore a unique tri-aspartic acid negative patch (134DDD136) identified in the prodomain of caspase-8. This patch resembles other charged patches previously identified as exosites in caspases-7 and -6 where they influence substrate selectivity and catalytic efficiency. Further, this patch forms a knob-like structure on the outside of the protein, revealing a capability to bind substrates. To assess this potential exosite, I will conduct cleavage and activity assays comparing between wild-type (WT) and mutant (134AAA136) caspase-8.  Cleavage assays indicate whether the presence of this patch improves substrate catalysis and peptide activity assays ensure that the active site remains intact and consistent through the two experiments. The results of this study could reveal whether or not this patch is an exosite and expand our knowledge about the structure and function of caspase-8, overall paving the way for better therapeutic interventions, such as substrate-selective inhibitors to diseases.