In the normal kidney, the Na+/H+ exchanger NHE1 interacts with phosphatidylinositol 4,5-bisphosphate—PI(4,5)P2—to maintain proximal tubule cell survival. However, research in mouse models has shown that glomerular injury leads to long-chain acetyl-CoA infiltration, which competes with PI(4,5)P2 for NHE1 binding and stimulates lipoapoptosis. Inhibition of long-chain acetyl-CoA synthesis in the proximal tubule protected these cells from apoptosis. Overall, the data suggest that the NHE1–PI(4,5)P2 interaction is disturbed in albuminuria and lipiduria via a reduced apoptotic threshold.