IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Also exhibits IGF-independent antiproliferative and apoptotic effects mediated by its receptor TMEM219/IGFBP-3R. Inhibits the positive effect of humanin on insulin sensitivity (PubMed:19623253). Promotes testicular germ cell apoptosis (PubMed:19952275). Interacts with XLKD1 (By similarity). Binds IGF2 more than IGF1. Forms a ternary complex of about 140 to 150 kDa with IGF1 or IGF2 and a 85 kDa glycoprotein (ALS). Interacts with humanin; humanin competes with importin KPNB1 for binding to IGFBP3, blocking IGFBP3 nuclear import and IGFBP3-mediated apoptosis (PubMed:14561895, PubMed:19623253, PubMed:26216267). Interacts with TMEM219. Expressed by most tissues. Present in plasma. IGFBP3 levels are higher during extrauterine life and peak during puberty. Up-regulated in the presence of IGF1, insulin and other growth-stimulating factors such as growth hormone, EGF and phorbol esters. The thyroglobulin type-1 domain mediates interaction with HN. Phosphorylated by FAM20C in the extracellular medium. The Singapore human mutation and polymorphism database