Our group works to advance understanding of catenin protein functions in cell and developmental contexts. While functionally distinct, p120-, delta-, plakophilin3- and ARVCF-catenin share some homology with beta-catenin. Each is present in multiple cellular compartments, and binds cadherin cell-cell adhesion proteins as well as nuclear factors. In the nucleus, beta-catenin is best known to activate gene targets after forming a complex with TCF/ LEF. In contrast, we and other labs find that the lesser-studied catenins bind different transcriptional regulators. For example, we most recently resolved p120's physical and functional association with the powerful REST and CoREST repressor complex, which makes differentiation decisions in stem cells. Other groups determined that p120 also binds the transcription factors Kaiso and Glis2. Intriguingly, despite such distinctions in binding mates, we find that p120-catenin and beta-catenin co-regulate certain genes central to development and cancer. In addition to this sub-group of shared down-stream gene targets, isoform1 of p120 is responsive at the protein level to upstream regulators likewise known to regulate beta-catenin stability. We posit that certain catenin isoforms evolved parallel although non-redundant functions in transducing Wnt signals to the nucleus. Regarding additional catenins, we determined that ARVCF-catenin is essential for vertebrate (frog) development and binds Kazrin, a little understood protein present at both junctions and the nucleus. We are also now testing for novel protein interactions of delta-catenin in other settings (e.g. synapse), and earlier reported that delta is cleaved to produce a large fragment that can enter the nucleus to bind and presumably regulate ZIFCAT, a transcriptional repressor. Recently, we resolved plakophilin3-catenin's interaction with ETV1, a transcriptional activator important in neural development. In keeping with our interest to reveal catenin functions in cell and developmental processes, we now aim to assess the extent to which catenin nuclear functions are networked or independent across the genome. Such insight will advance our understanding of the many developmental and pathologic processes subject to modulation by Wnt and additional catenin-dependent pathways.