During the development of multicellular organisms, integrins act through integrin-associated molecules to regulate essential aspects of cell-cell and cell-matrix adhesion, cell polarity and cell survival. On p. 2913, Reinhard Fässler and co-authors report that the integrin-associated protein PINCH1 regulates all four of these processes during the peri-implantation stage of mouse development. PINCH1 interacts with integrin cytoplasmic tails at focal adhesions via integrin-linked kinase (ILK). The authors show that, like β1-integrin- and Ilk-deficient mice, mouse embryos carrying a disrupted PINCH1 gene arrest at the peri-implantation stage. To pinpoint this phenotype, the authors examined embryoid bodies (EBs), an experimental model for this stage of development. Although PINCH1-null EBs show many of the same defects as β1-integrin- and Ilk-mutant EBs (including abnormal epiblast polarity and detachment of cells from matrix), they also exhibit abnormal cell-cell adhesion and increased endodermal apoptosis. Thus, the authors conclude, PINCH1 acts in both an ILK-dependent and an ILK-independent manner during mouse peri-implantation.