Significance The cellular functions of epithelia rely on their polarized architecture. Loss of their polarity is often associated with carcinoma progression and tumor metastasis. The basement membrane (BM), a specialized sheet of the extracellular matrix, secreted basally by most epithelia, plays an important role in the establishment and maintenance of epithelial cell polarity. However, the process of BM-polarized secretion is not well understood. In this study, we show that a significant decrease of the phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) results in BM protein secretion on both the apical and the basal side of the epithelium. Together, our data indicate a specific role for PIP2 in the organization of epithelial architecture by restricting the deposition of BM proteins to the basal side.