Although the malaria parasite develops within erythrocytes, it has to modify the surrounding red blood cell membrane for its intracellular survival and maturation. These changes include the translocation of proteins across the parasite and the parasitophorous vacuole membranes to the host membrane. In this review, Denise Mattei, Katherine Hinterberg and Artur Scherf focus on two distinct giant parasite molecules of unprecedented size (approximately one MDa), called Pf332 and PflI-I, that are synthesized and exported into the cytoplasm of the host cell in the asexual and sexual blood stages of Plasmodium falciparum, respectively. The corresponding genes are located in genetically unstable subtelomeric chromosome regions.