Function
This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. It is an important modulator of extracellular signals, including those elicited by E-cadherin-mediated cell-cell adhesion, which plays an important role in maintenance of the structural and functional integrity of epithelia. In addition to its role in promoting assembly of adherens junctions, the protein is thought to play a pivotal role in the regulation of cytotoxicity in NK cells. The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. More recently, this gene has been shown to be a critical myeloid-restricted vulnerability in Acute Myeloid Leukemia (AML). Its targeting, either by the small-molecule inhibitor IPI-549 or by a first-in-class proteolysis-targeting chimera (PROTAC) named ARM165, has been shown to reduce AML cell progression both in vitro and in vivo.