5T4, also known as Trophoblast glycoprotein and Wnt-activated inhibitory factor 1 （WAIF1）, is a single-pass transmembrane protein which may function as an inhibitor of Wnt/beta-catenin signaling. It has been identified that TIP-2/GIPC, a common interacting protein involved in cancer, interacts with 5T4 through its PDZ domain. 5T4 inhibits Wnt/ beta -catenin signaling by binding to LRP6 and inhibit Wnt-induced LRP6 internalization into endocytic vesicles. Conversely, 5T4 can activate noncanonical Wnt signaling through DKK1. In addition to LRP6, in-house data indicates 5T4 can also interact with Frizzled8.