Reticulon and REEP family of proteins stabilize the high curvature of endoplasmic reticulum (ER) tubules. P. berghei Yop1 (Pb Yop1) is a REEP5 homolog in Plasmodium . Here we characterize its function using a gene‐knockout (Pb yop1∆). Pb yop1∆ asexual stage parasites display abnormal ER architecture and an enlarged digestive vacuole. The erythrocytic cycle of Pb yop1∆ parasites is severely attenuated and the incidence of experimental cerebral malaria is significantly decreased in Pb yop1∆‐infected mice.