Here we show that paralogs of a mosquito LRR gene family, APL1, display distinct activities against different species of the genus Plasmodium. Each APL1 paralog is required for the full protection of mosquitoes against only one of the two malaria parasite lineages tested, and each APL1 paralog protects by involvement in only one of two separate immune signalling pathways. This evidence concerns the gene ADI1 and malaria.