Phosphatidylethanolamine-binding protein (PEBP) is a cytoplasm soluble protein with a high conserved structure. It has been approved recently that PEBP is a multifunctional molecule regulating several important cellular signal pathways, including ERK cascade, NF-κB pathway, and signaling of G protein-coupled receptors. Furthermore, the role of PEBP in tumor metastasis also got a comprehensive attention in the field of clinical cancer research. Together, as a signal regulator at multiple paths in cell, PEBP is becoming a new focus in several research fields. This review is aimed to introduce the newest biological progress on PEBP.