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Secreted Wnt proteins play essential roles in many biological processes during development.Abnormal Wnt signaling is associated with many cancers.Although intensive studies have identified many components involved in Wnt reception, little is known about the mechanism(s) controlling Wnt secretion.Recent studies have identified Wntless (Wls) as an essential component for Wnt secretion in Wnt-producing cells.In addtion, retromer complex has been shown to be essential for Writ signaling in Wnt-producing cells.However, currently it is unclear whether retromer controls Wnt signaling by regulating Wnt secretion.To determine the molecular mechanism(s) by which retromer controls Wnt signaling, we generated mutant for Vps35, an essential retromer subunit in model system Drosophila.We have examined a role of Vps35 in Wnt signaling in both Drosophila and mammalian cancer cells.Here, we provide compelling evidence that the retromer activity is required for Wnt secretion.Importantly, Vps35 co-localizes and forms a complex with Wls in endosomes.Wls becomes unstable in the absence of the retromer activity.Furthermore, we show that Wls levels are regulated by dynamin-mediated endocytosis process.Our new findings have linked VWls and retromer in the same Wnt secretion pathway.We propose that retromer complex controls Wnt secretion by recycling Wntless from endosomes to the trans Golgi network (TGN).