PH-interacting protein (PHIP) binds to the PH domain of IRS-1 (insulin receptor substrate-1), which is a major substrate of the insulin receptor tyrosine kinase and is essential many biological process including mitogenesis, gene expression, and glucose transport [, ]. It regulates insulin receptor-stimulated GLUT4 translocation in skeletal-muscle cells. Its WD40 repeat-containing isoform, PHIP1, localises exclusively in the nucleus in the pancreatic beta cell and is a positive regulator of beta-cell function [].
