Tight junctions are key componet of cell-cell junctional complexes in epithelial and endothelial cells. Tight junction proteins participate in the control of the diffusion of molecules through the paracellular pathway, act as an intramembrane diffusion barrier for lipids between the apical and basolateral cell surface domains, as well as function in the regulation of cell proliferation and gene expression. We have identified and characterized several TJ-associated signalling complexes that contain different types of signalling proteins, such as ZONAB, a ZO-1-interacting nucleic acid binding protein, RhoGTPase activators such as GEF-H1 and p114RhoGEF, and the Rho GAP SH3BP1. Results will be discussed that disclose further molecular mechanisms on how tight junctions regulate paracellular permeability, cell proliferation and survival, as well as transcriptional and postranscriptonal modes of gene expression.