Phosphatidylinositol-4-phosphate-5-kinase (PIP5K) and phosphatidylinositol-5-phosphate-4-kinase (PIP4K) are two families of lipid kinases that catalyze production of phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). The majority of cellular PI(4,5)P2 is produced by PIP5Ks, using PI(4)P as a substrate. In a non-canonical pathway, PIP4Ks catalyze the conversion of PI(5)P into PI(4,5)P2, but the importance of PIP4K has remained unclear. Unexpectedly, we find that PIP4K has a kinase independent role in regulating cellular PI(4,5)P2 levels. We demonstrate that PIP4Ks act as negative regulators of PIP5Ks and that depletion of PIP4K causes hyperactivation of PIP5Ks. Increased cellular PI(4,5)P2 generation by PIP5Ks promotes flux through the PI3K pathway, and these effects are reversed by reconstitution with kinase-dead PIP4K. This novel role for PIP4Ks provides an additional mechanism by which these kinases regulate cellular metabolism, which has the potential to be exploited by therapeutics.