Updated publication reference for PubMed record(s): 31348803. In the absence of an effective vaccine and the emerging resistance to artemisinin combination therapy, malaria is still a significant threat to human health. Increasing our understanding of the specific mechanisms of the biology of Plasmodium is essential to propose new strategies to control this infection. Here, we demonstrated that GEXP15, a specific protein in Plasmodium, was able to interact with the PP1 and regulate its phosphatase activity. We showed that both proteins are implicated in common protein complexes involved in the mRNA splicing and proteasome pathways. We reported that the deletion of GEXP15 leads to a loss of parasite virulence during asexual stages and a total abolishment of the capacity of deficient parasites to develop into oocysts. We also found that this deletion affects both protein phosphorylation status and significantly decreases the expression of essential proteins in schizont and gametocyte stages. This study characterizes for the first time a novel molecular pathway through the control of PP1 by an essential and specific Plasmodium regulator, which may contribute to the discovery of new therapeutic targets to control malaria.