Plasmepsin, an aspartic protease present in the vacuole, attacks the hemoglobin molecule first before falcipain, a cysteine protease, separates the large pieces into minute peptides . Since intact hemoglobin cannot be broken down by falcipain without first being denatured, the first cleavage by plasmepsin is essential for hemoglobin degradation. It is thought that this cleavage causes the haemoglobin molecule to disassemble, effectively facilitating subsequent proteolysis . SUB1, a serine protease that resembles subtilisin, has been shown to promote egress . Minutes before egress, the still intracellular merozoite releases a SUB1 from specialized secretory organelles known as exonemes as a result of a calcium and cGMP-dependent signal . One of the most abundant merozoite surface and parasitophorous vacuole resident soluble proteins that are proteolytically changed by SUB1 upon release into the vacuole lumen is SERA6, a potential cysteine protease implicated in egress and invasion . When SUB1 discharge or catalytic activity is pharmaceutically suppressed, released merozoites are prevented from exiting and/or their capacity to infiltrate the host is lowered . A new class of antimalarial therapies is urgently needed to combat the parasite's rising drug resistance, and drugs that target SUB1 activity should have potential as a new class of antimalarial therapeutics .