Dynamic changes in epithelial cell-cell adhesion and motility are crucial for branching morphogenesis – the process by which highly branched epithelial organs, such as the lung and kidney, grow and develop from a simple epithelial bud. Although many key regulatory factors involved in branching morphogenesis have been identified, it remains unclear how they coordinate to control epithelial cell dynamics. In this issue (p. 2200), the Yamada laboratory presents strong evidence for the essential role of Btbd7 in orchestrating epithelial remodelling during branching morphogenesis in the mouse lung, kidney and salivary glands in vivo. Specifically, the authors show that loss of Btbd7 in a knockout mouse model results in increased cadherin localisation to cell-cell junctions and reduced motility in the outer cells of epithelial buds. Conversely, Btbd7 overexpression in vitro leads to decreased cell-cell adhesion and increased cell motility. They further show that Btbd7 induces E-cadherin ubiquitination, internalisation and degradation in MDCK epithelial cells, providing a mechanism for how Btbd7 can control cell adhesion and migratory behaviour. Collectively, these data establish for the first time that the new regulatory molecule Btbd7 is required for successful in vivo branching morphogenesis of salivary gland, lung and kidney.