Caspases are the protein hitmen of the cell, cutting key protein substrates and causing a controlled and coordinated cell death. Their regulation is critical for proper development, inflammation responses, and differentiation. Malfunctions in caspase activity and the apoptotic pathway play a role in cancer and neurodegenerative diseases. This study dives into the regulation of a particular executioner caspase, caspase-7, and how phosphorylation of this protein regulates its function. By taking an interdisciplinary approach utilizing molecular biology, protein biochemistry, enzymology, and crystallography we have shown that an engineered caspase-7 phosphorylation mimic inactivates the protein by sterically preventing substrate binding.