Epithelial cells form the lining of cavities and the surfaces of organs and blood vessels in animals. A distinctive feature of epithelial cells is their polarization, as indicated by the segregation of cell cortex proteins into functionally distinct regions. In particular, epithelia have apical and basolateral domains separated by tight junctions that attach the cells to one another. Par3 is a large scaffold protein that is localized to the lateral membrane close to the tight junction. Although many Par3 binding partners are known, its function is not fully understood. Recently, Vanderbilt Basic Sciences investigator Ian Macara reported that Par3 is necessary for the survival of mammary epithelial cells. Now, he and his postdoctoral fellow Syed Mukhtar Ahmed, show that Par3 serves as a receptor for the exocyst, an eight subunit protein complex that tethers exocytotic vesicles to the lateral plasma membrane. Macara and Ahmed began their journey by trying to explain why knockdown of Par3 expression using RNAi techniques caused mammary epithelial cells to undergo death by apoptosis. They soon discovered that the activity of an anti-apoptotic protein kinase, AKT, was reduced in Par3 deficient cells. This then led them to discover that the cells also lacked normal levels of PIP3, a membrane lipid required for activation of AKT. PIP3 is generated by the enzyme PI 3-kinase, which is one of many proteins carried to the membrane by the exocyst as part of the E-cadherin:β-catenin complex. Further studies demonstrated that Par3 binds directly to one of the exocyst subunits, and the researchers were able to identify the specific region of Par3 required for this interaction. Expression of this small piece of the Par3 protein in Par3 deficient cells reversed many of the effects of Par3 deficiency and protected the cells from apoptosis. These findings provide important new insight into Par3 function and reveal how the exocyst docks at the tight junction region of the plasma membrane. They also provide important new information about mammary cell function and survival. The work is published in the journal Nature Communications [S. M. Ahmed & I. G. Macara., (2017) Nat. Commun., 8, 14867].