Cell division requires that the orientation of the mitotic spindle be established correctly because many processes, such as the formation of epithelia, rely on the spindle being aligned in a particular direction. Now, Angeliki Malliri and colleagues (Porter et al., 2019) investigate the role of Dlg1, a previously identified spindle orientation factor, in mammalian epithelial cells. Dlg1 knockdown in MDCKII cells disrupts the establishment of a single lumen that is observed when these cells are seeded in 3D matrices. Furthermore, whereas wild-type cells usually orient their spindles orthogonally to the apical surface, the authors show that spindles of Dlg1 knockdown cells orient in a random fashion, thus providing a probable reason for defective lumen formation. They demonstrate that Dlg1 binds the membrane-associated protein CASK, which localises Dlg1 to basolateral domains, and show that CASK itself is required for correct spindle orientation. Disruption of the Dlg1–CASK interaction phenocopies Dlg1 or CASK depletion, suggesting that this interaction is required for establishing oriented cell division. Indeed, both Dlg1 and CASK, as well as the Dlg1–CASK interaction, are also essential to localise the LGN–NuMA complex, which regulates spindle orientation by orchestrating the action of astral microtubules and dynein motor proteins. Together, these results reveal the critical importance of Dlg1–CASK binding for spindle orientation, which has important implications for the correct formation of epithelia.

• © 2019. Published by The Company of Biologists Ltd