Schekman explains how his laboratory used baker’s yeast to uncover major proteins involved in the secretory pathway, and describes proteins involved in budding, vesicle trafficking, and vesicle fusion.  Schekman also presents data from his laboratory that helped to identify the ER channel through which proteins enter the secretory pathway. These series of experiments show how, step by step, scientific knowledge evolves, uncovering the fundamental mechanisms to better understand human disease.