Connexin 43 (Cx43) is a gap junction protein that is expressed in many tissues of the body. There is mounting evidence in bone cells, however, that Cx43 can form intracellular signalling nodes, which are scaffolded around the Cx43 C-terminus domain. Using a mouse model of Cx43 C-terminus truncation, Joseph Stains and colleagues test the hypothesis that the Cx43 C-terminus is a docking platform for signalling proteins and is required for efficient downstream signalling in bone (p. 531). The authors examine the skeletal phenotype induced by Cx43 C-terminus truncation, finding that, in male mice, the phenotype is nearly identical to that reported for conditional deletion of the entire Cx43 gene in bone cells. Moreover, the authors show that the Cx43 C-terminus interacts with the signalling proteins PKCδ, ERK1/2 and β-catenin, all of which are required for optimal osteoblast function. Truncation of the Cx43 C-terminus impairs signal cascade activation, which impacts on osteoblast proliferation, differentiation and collagen processing. These data show that the Cx43 C-terminus binds signalling proteins and is required for both efficient signalling and osteoblast differentiation. In addition to exchanging signals, therefore, Cx43 C-terminus-containing gap junctions may also be required to recruit the appropriate effector molecules to the Cx43 C-terminus to modulate cell function and bone acquisition.