Malaria is a devastating global disease caused by protozoan parasites of the genus Plasmodium. The disease leads to around half a million deaths annually and is a major contributor to global poverty. Clinical malaria results from replication of asexual blood stage parasites within circulating red blood cells. Successive cycles of intraerythrocytic replication leads to active egress of merozoites with associated host red blood cell destruction, and invasion of fresh red cells. Both egress and invasion involve the activity of essential parasite proteolytic enzymes, leading to interest in these enzymes as potential new drug targets. In this talk I will focus on invasion, a poorly-understood process that involves the induced formation of a parasitophorous vacuole into which the parasite moves. Immediately following invasion, the nascent vacuole membrane seals and pinches off behind the newly invaded parasite through an unknown mechanism, enclosing the parasite within the host cell. During erythrocyte invasion, several abundant merozoite surface proteins are shed by a membrane-bound subtilisin-like protease called SUB2. I will describe our accumulated knowledge of the role of the SUB2 in invasion, including recent data indicating that SUB2 ‘sheddase’ activity at invasion is critical for sealing the host erythrocyte membrane following parasite internalisation and for the correct functioning of several merozoite surface proteins.