Updated project metadata. The Wnt signaling pathway is playing a crucial role during development and adult tissue homeostasis. However, the tissue and cell type-specific regulation of Wnt pathway activity remains incompletely understood. Here we identify FOXB2, an uncharacterized forkhead box family transcription factor, as a potent activator of Wnt signaling in normal and cancer cells. Proximity-dependent biotinylation assay (BioID) coupled with mass spectrometry identified transcriptional co-regulators required for FOXB2-dependent Wnt activation.