IGFBP-3 (Insulin-like growth factor binding protein-3) modulates the biological activity of IGF. It circulates in a ternary complex with IGF and the acid-labile subunit (ALS). Proteolysis of IGFBP-3 by tissue plasminogen activator (tPA), a disintegrin and metalloproteases (ADAMs), and prostate specific antigen (PSA) contributes to IGFBP-3 degradation or a reduction in its affinity for IGF. The majority of soluble IGFBP-3 found in circulation is secreted from hepatic non-parenchymal cells. IGFBP-3 potentiates EGF-EGFR-mediated cell growth, modulates adipogenesis, and regulates TGF-beta signaling, DNA damage, apoptosis, autophagy, and gene transcription.