OCRL is an inositol polyphosphate 5-phosphatase encoded on chromosome X that catalyzes hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol-3,4,5-bisphosphate 1. This enzyme preferentially acts on PtdIns(4,5)P2 and also hydrolyzes inositol 1,4,5-trisphosphate and inositol 1,3,4,5-tetrakisphosphate. OCRL localizes to the trans-Golgi network and regulates phosphoinositide pools at endosomes, playing critical roles in endosomal trafficking, primary cilia assembly, and phagocytosis by attenuating PI3K signaling 2. OCRL mutations cause two X-linked renal diseases: Lowe syndrome (oculocerebrorenal), a severe multisystem disorder characterized by congenital cataracts, central hypotonia, intellectual disability, and renal Fanconi syndrome 3, and the milder Dent disease 2, manifesting primarily as proximal tubule dysfunction with proteinuria, hypercalciuria, and nephrolithiasis 4. The kidney is particularly vulnerable to OCRL loss because it depends strictly on phosphoinositide-regulated processes including cell polarization, filtration, and solute reabsorption 5. Understanding OCRL's role in phosphoinositide homeostasis along the endolysosomal pathway is fundamental to developing treatments for these conditions 2.