Plasmodium falciparum causes the most severe form of malaria in humans causing over 700,000 deaths each year. Invasion of human erythrocytes is essential for its survival and this process involves the interaction of multiple host-parasite receptor-ligand interactions. One of the most important is that of the parasite ligand PfRh5 with the host receptor basigin.  PfRh5 is the leading blood-stage vaccine candidate that elicits potent strain-transcending invasion inhibitory antibodies. We have determined the crystal structure of PfRh5 to a resolution of 2.18 Å (Chen et al., PNAS 2014).  The PfRh5 adopts a novel fold with the core structure consisting of seven α-helices winding around two β-sheets in an anti-parallel fashion to form a flat and compact molecule.  Chemical cross-linking mass spectrometry and molecular modelling of the PfRh5-basigin interaction suggested that the receptor binds at one end of PfRh5, providing other areas for interaction with other proteins, such as PfRh5 interacting protein, PfRipr1 (RH5-interacting protein 1).  Quantitative MS analyses of Co-IPs using HA-tagged PfRipr1 or pull-downs using recombinant Rh5 as a bait demonstrated that PfRH5 and PfRipr 1 associates with a novel conserved protein (PfRipr2) to form a complex on the merozoite surface.  This discovery elucidates a novel protein that may tether PfRH5 to the merozoite surface and facilitate its binding with basigin.  Our insights open potential avenues for novel anti-malarial strategies that may inhibit the formation of the crucial basigin-PfRH5-PfRipr1/2 invasion complex.