胰岛素样生长因子结合蛋白家族(IGFBPs)份额50%与守恒的N末端氨基酸的身份和C末端区域负责绑定胰岛素样生长因子I和II (IGF I和IGF II)。大多数循环IGF与IGFBPs复合物,这被认为增加体内IGF的住所,调节igf的可用性以靶向igf受体，减少igf的胰岛素样效应，并作为独立于igf的信号分子。约75%的循环igf存在于1500 220 KDa伴IGFBP3和ALS的复合物中。这种复合物太大，无法通过内皮屏障。其余的20 - 25%的igf以40 - 50 KDa复合物的形式与其他igfbp结合。IGF:IGFBP复合物通过IGFBP的蛋白水解释放IGF。igf在释放后会变得有活性，但当与某些igfbp结合时，igf也可能有活性。IGFBP1在羊水中富集，并在胰岛素控制下在肝脏中产生(胰岛素抑制其产生)。IGFBP1的结合刺激IGF功能。目前尚不清楚是否有蛋白酶降解IGFBP1。 IGFBP2 is enriched in cerebrospinal fluid; its binding inhibits IGF function. IGFBP2 is not significantly degraded in circulation. IGFB3, which binds most IGF in the body is enriched in follicular fluid and found in many other tissues. IGFBP 3 may be cleaved by plasmin, thrombin, Prostate specific Antigen (PSA, KLK3), Matrix Metalloprotease-1 (MMP1), and Matrix Metalloprotease-2 (MMP2). IGFBP3 also binds extracellular matrix and binding lowers its affinity for IGFs. IGFBP3 binding stimulates the effects of IGFs. IGFBP4 acts to inhibit IGF function and is cleaved by Pregnancy associated Plasma Protein A (PAPPA) to release IGF. IGFBP5 is enriched in bone matrix; its binding stimulates IGF function. IGFBP5 is cleaved by Pregnancy Associated Plasma Protein A2 (PAPPA2), ADAM9, complement C1s from smooth muscle, and thrombin. Only the cleavage site for PAPPA2 is known. IGFBP6 is enriched in cerebrospinal fluid. It is unknown which if any protease degrades IGFBP6.