As part of its life cycle, the malarial parasite Plasmodium falciparum replicates in host erythrocytes, and daughter merozoites are released via a highly regulated and calcium-dependent process. The serine protease SUB1 is discharged shortly before egress to cleave parasite proteins that are required for erythrocyte exit and invasion. Withers-Martinez et al. now solve the crystal structure at 2.25 Å of the enzymatically active core domain of P. falciparum SUB1 partially bound to its prododomain and complexed with a monoclonal antibody Fab fragment. The structure reveals the architecture of the substrate cleavage site and also identifies a labile, redox-sensitive disulphide bridge near the active site that regulates SUB1 activity. Thus, although not the native protein, this structure provides mechanistic insights that could be useful for the design of new antimalarial drugs.