At the intersection of cell biology, genetics, and molecular biology, this case study examines the complexities of vesicular transport and the potentially large-scale implications on human health in instances of dysregulation. Students analyze and evaluate the molecular, clinical, and ethical aspects of COPA syndrome, a rare autosomal dominant disease with incomplete penetrance that results from a mutation in the COPI coatomer complex affecting retrograde vesicular transport. In Part I of the case, students read about an actual child with COPA syndrome, learn about the implications of this genetic disease, and discuss ethical issues related to genetic testing. In Part II, students review the vesicular transport system and the relationship between protein structure and function, and then generate hypotheses to explain different clinical phenotypes. In Part III, students draw connections between COPA syndrome and other rare diseases. The case is suitable for a variety of biology courses in which students already have a solid understanding of basic cellular and molecular biology concepts, including intracellular transport and mechanisms of inherited disease.