Malaria is one of the three most lethal infectious diseases. Unlike AIDS and tuberculosis, malaria is unique in that the parasite must complete a complex differentiation program in its mosquito vector for transmission to occur (1) (Fig. 1). Despite significant progress made in the last couple of decades, our mechanistic understanding of how the parasite develops in the mosquito is incomplete. A very strong bottleneck occurs in the mosquito gut (2). Out of the many hundred gametocytes that are typically ingested by the mosquito with an infected blood meal, only few parasites (single digits) succeed to form oocysts, even in high-transmission areas. As such, the parasite’s midgut stages constitute prime targets for interference with gut traversal and for curtailing transmission.