The adaptor protein NHERF1/EBP50 (Na/H exchanger regulatory factor 1/ezrin-radixin-moesin-binding phosphoprotein 50) emerged recently as an important player in breast cancer progression. Consisting of two tandem PDZ domains linked to a carboxyl-terminal ezrin-binding region, NHERF1 assembles macromolecular complexes at the apical membrane of epithelial cells in many epithelial tissues, including the mammary gland. Involved initially in trafficking and regulation of transmembrane ion transporters and G protein-coupled receptors, NHERF1 also couples molecules involved in cell growth, such as the platelet-derived growth factor receptor (PDGFR) and PTEN (phosphatase and tensin homolog deleted on chromosome 10). In the previous issue of Breast Cancer Research, Pan and colleagues show an inhibitory action of NHERF1 on the phosphoinositide-3 kinase (PI3K)/Akt pathway in breast cancer cells via interaction of NHERF1 with PTEN, the physiological antagonist of the PI3K. Additionally, they show that NHERF1 expression confers susceptibility to PDGFR pharmacological inhibition depending on the presence of PTEN tumor suppressor.