From molds to mammals, glucose is the most important fuel for life on earth. The rate-limiting step for the utilization of glucose is its uptake into cells. Mammals have fourteen different sugar transporters belonging to the SLC2A family, referred to as GLUTs. GLUT transporters have varied tissue expression and kinetics, and their activities must be synchronized and regulated for the appropriate whole-organism-wide distribution of glucose and other sugars. Here, I will present our multidisciplinary approach that has revealed important insights into the mechanism of glucose (GLUT) uptake. I will also present our recent structural insights into the transport of ATP into the ER, which is a pathway that is essential for protein folding, quality control and trafficking.