The process of protein translation and translocation into the endoplasmic reticulum (ER) can often be challenging for introductory college biology students to visualize. To help them understand how proteins become oriented in the ER membrane, I developed a hands-on activity in which students use Play-Doh to simulate the process of protein insertion into the ER membrane. After completing the hands-on activity, students are better able to solve problems in which they have to predict the membrane orientation of a protein.