Polarised exocytosis ensures delivery of membrane and proteins to a defined point on the plasma membrane. Together with vesicle-associated proteins, lipids−such as phosphatidylinositol phosphates (PIPs)−are important facilitators of exocytosis. Oxysterol-binding protein (OSBP) homologues comprise the Osh protein family in S. cerevisiae and are needed for polarised exocytosis, cell growth and polarisation. Whereas Osh proteins bind lipids, it is unclear whether this interaction is important for exocytosis. Now, Keith Kozminski and co-workers (p. 3891) show that this activity of Osh4p depends on the lipid ligands PIP4 and sterol; Osh4p regulates the last steps of the exocytic pathway that supports polarised cell growth. The binding of PIP4 to Osh4p supports docking of vesicles at the plasma membrane, and competitive binding between PIP4 and sterol is likely to regulate the association of Osh4p with excoytic vesicles. The authors report that another Osh protein, Osh6p, also depends on lipids for its support of polarised exocytosis. On the basis of their data, they propose a two-step model on how Osh proteins contribute to the creation docking-competent vesicles, and the successful vesicle docking and fusion with the plasma membrane after lipid exchange.