It was previously known that some strains of the malaria parasite Plasmodium falciparum can evade the immune system of the mosquito vector Anopheles gambiae. A new study from Carolina Barillas-Mury and colleagues (Science doi:10.1126/science.1235264, 9 May 2013) identifies the first P. falciparum gene that enables the parasite to infect mosquitoes without activating their immune system. The authors analyzed a genetic cross between two P. falciparum lines that differed in their ability to infect wA. gambiae and mapped a quantitative trait locus (QTL) to a 172-kb region that encompassed 41 genes. Analysis of gene expression and sequencing reduced the number of candidates, and the authors made knockouts of the two top candidate genes, Pfs47 and Pfs48/45, which both encode 6-cysteine protein family members. Parasites with Pfs48/45 knockout that invaded the midgut of the mosquito had a similar phenotype to wild-type parasites, showing that this gene is not needed to evade the mosquito immune system. In contrast, Pfs47 knockout parasites invaded the midgut but were eliminated by mosquitoes, showing that this gene is essential in evading the mosquito's immune system. The authors were also able to complement Pfs47 knockout with different Pfs47 alleles, suggesting that this gene's function increases parasite survival in A. gambiae.