The long and winding road: On the endoplasmic reticulum of Plasmodium and implications for pathogenesis

As a eukaryote, Plasmodium , the causative agent of malaria, is reliant on its endoplasmic reticulum (ER) for survival. However, as a protozoan pathogen, Plasmodium has also adapted its ER to support its parasitic lifestyle. This Pearl focuses on the interplay between conserved ER functions in Plasmodium such as cell signaling, protein synthesis/secretion, lipid production, and cellular stress, and their contribution to parasite pathogenesis. We further summarize the current knowledge about the role of the ER in pathogenic processes such as motility, egress/invasion, host-cell remodeling, and transmission throughout the blood, liver, sexual, and mosquito stages. Collectively, we hope that discussing the Plasmodium ER as both a conserved cellular hub and a source of parasite-specific biology offers promising opportunities for antimalarial strategies.