Phosphoglucose isomerase (PGI) is a glycolytic enzyme that exhibits a dual function as an extracellular cytokine, under the name autocrine motility factor (AMF). Its cell surface receptor, gp78/AMFR, is also localized to the endoplasmic reticulum where it functions as an E3 ubiquitin ligase. Expression of both AMF/PGI and gp78/AMFR is associated with cancer and, in this review, we will discuss various aspects of the biology of this ligand-receptor complex and its role in tumor progression.