Using Pompe disease as a context affords the opportunity for students to consider multiple biological concepts and embraces the Next Generation Science Standards Disciplinary Core Ideas Structure and Function (LS1.A) and Inheritance of Traits (LS3.A) as well as Crosscutting Concepts Structure and Function and Cause and Effect. These crosscutting concepts are very much interrelated as we consider progression of disease from the molecular to the organismal level. The concepts are repeatedly emphasized, providing "explicit instructional support" for students to "develop a cumulative, coherent, and usable understanding of science and engineering." DNA, proteins, enzymes, genetics, and human disease are taught together through the story of patients with Pompe disease as students engage in a simulated clinical assay and genetic analysis and present their findings in grand rounds. The activity is one of multiple lessons sequenced to scaffold student understanding of clinical and translational science, starting with a first-person perspective of a father who loses his infant son to Pompe and concluding with a role play based on actual events surrounding approval of human clinical trials of gene therapy for Pompe disease.