INPP5B is an inositol 5-phosphatase that regulates cellular signaling by hydrolyzing phosphate groups from phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) to produce PI(4)P, and from inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) 1. The enzyme functions across multiple cellular compartments including the cytosol, plasma membrane, and primary cilia, where it modulates PI(4,5)P2-dependent processes 1. INPP5B plays critical roles in B cell receptor clustering and signaling by dephosphorylating PI(4,5)P2, which enables actin disassembly and BCR mobilization through increased cofilin-mediated actin severing 2. It also participates in primary cilia formation, with deficiency causing cilia development defects in cultured cells and zebrafish models 3. INPP5B interacts with the small GTPase RAB18 and may influence sterol mobilization and cholesterol biosynthesis 4. In spermatogenesis, INPP5B deficiency in mice results in reduced fertility 5. While INPP5B shares structural similarity with OCRL (mutated in Lowe syndrome), no disease-causing INPP5B mutations have been reported in humans 1. Species-specific differences exist between mouse Inpp5b and human INPP5B in transcription and splicing patterns, suggesting divergent compensatory roles for OCRL deficiency 6. Recent genetic studies identified INPP5B as associated with migraine risk, though mechanistic details require further investigation 7.