<p>by Allison Cohen, Tim Bergner, Amandine Guérin, Maryse Lebrun, Michael Laue, Christian Klotz, Boris Striepen</p> The apicomplexan parasite <i>Cryptosporidium</i> is a leading cause of diarrheal disease in young children. Within the intestinal epithelium, <i>Cryptosporidium</i> establishes a unique intracellular niche in the apical brush border of enterocytes. A structurally complex interface between host and parasite acts as a holdfast and enables protein and metabolite transport. How the parasite invades its host cell and builds the interface is poorly understood. Here, we reveal parasite invasion with high temporal and spatial resolution using rigorous molecular markers. We find that sequential discharge of specialized secretory organelles anchors the parasite within the host prior to internalization. The single <i>Cryptosporidium</i> rhoptry persists beyond its initial pre-invasion discharge, acting as a conduit for the secretion of multiple waves of effector proteins. Ultimately, the rhoptry membrane gives rise to the feeder organelle that separates host from parasite cytoplasm. These findings lead us to propose a mechanistic model of <i>Cryptosporidium</i> invasion and intracellular parasitism.