Insulin-like growth factor-binding protein 4 (IGFBP-4) inhibits the actions of IGF-I and IGF-II. The distribution of IGFBP-4 in tissues is dependent on its glycosylation state, however it preferentially targets connective tissue (Firth and Baxter; Qin et al.). IGFBP-4 is also produced in liver, adrenal glands, Leydig cells, developing embryos, spinal cord, and thymic cortex. IGFBP-4 inhibits WNT/β-catenin signaling, which downregulates prostate cancer proliferation (Zhu et al.). In vitro studies suggest that IGFBP-4 inhibits proliferation of neuroblastoma and glioma, while promoting bone loss in osteosarcoma and multiple myeloma (Durai et al.).