Inositol polyphosphate-5-phosphatase E (INPP5E)

Inositol polyphosphate-5-phosphatase E (INPP5E) is an enzyme encoded by the INPP5E gene located on chromosome 9 in humans. Its protein product (72 kDa, 644 amino acids) localizes primarily to the primary cilium, a specialized organelle involved in various signaling pathways and cellular processes. INPP5E's main function is to hydrolyze critical phosphoinositides—including phosphatidylinositol-3,4,5-trisphosphate and phosphatidylinositol-4,5-bisphosphate—regulating the balance of membrane lipids to control signal transduction, cell cycle progression, ciliogenesis, and cellular homeostasis. It is crucial for ciliary growth, stability, and the maintenance of cell signaling pathways such as the phosphoinositide 3-kinase (PI3K/AKT) and Sonic Hedgehog (Shh) cascades. INPP5E interacts with a network of ciliary proteins (such as ARL13B, PDE6D, CEP164, RPGR, and TULP3) and affects diverse physiological activities, including autophagy, immune cell behavior, vesicular trafficking, and chromosomal integrity during mitosis. Mutations in INPP5E are causative for several human disorders, most notably Joubert syndrome, Meckel–Gruber syndrome, and MORM syndrome, as well as inherited retinal dystrophy. Loss of INPP5E activity leads to multiorgan dysfunction, ciliary instability, and aberrant developmental signaling. There are no approved drugs known to interact directly with INPP5E; however, its disease associations make it a potential future therapeutic target, particularly in congenital ciliopathies and select cancers.

Other names

Phosphatidylinositol-4,5-bisphosphate 5-phosphatase EPharbin72 kDa inositol polyphosphate 5-phosphatasePhosphatidylinositol-3,4,5-trisphosphate 5-phosphatasePhosphatidylinositol polyphosphate 5-phosphatase type IVCORS1CPD4JBTS1MORMSPPI5PIV