Wnts are secreted signaling proteins that play a central role in development, adult tissue homeostasis and cancer. In the past decade, detailed insight has been gained into the signaling pathways that are triggered by Wnts, but how Wnts are secreted from producing cells and how this process is regulated to control signaling activity is still largely unexplored. Recent studies have shown that Wnt secretion is mediated by a dedicated secretory pathway. A central player in this pathway is the Wnt binding protein Wntless (Wls), which transports Wnt from the Golgi to the cell surface for release. Because Wls is a limiting component in the pathway, it needs to be recycled back to the Golgi to maintain Wnt secretion. We have shown that this is mediated by the retromer, a multi-subunit trafficking complex that transports endocytosed Wls from endosomes to the trans-Golgi network (TGN). Importantly, we recently found that Wls retrieval requires a novel, SNX3-dependent retromer pathway that segregates Wls into vesicular carriers that are morphologically distinct from the tubular transport carriers that are formed by the classical retromer pathway. To gain further mechanistic insight into this key step in the Wnt secretion pathway, we will investigate how these vesicular carriers are formed, how they dock at the TGN and how Wls is specifically sorted into this novel transport pathway. Detailed insight into this mechanism will contribute to our understanding of the Wnt secretion pathway and will identify potential new drug targets for the therapeutic inhibition of Wnt secretion in cancer.