IGFBP3 and amyotrophic lateral sclerosis: Circulating IGF-1 binds mainly to IGF-binding protein 3 (IGFBP-3) and IGF-binding protein 5 (IGFBP-5), which in turn form a ternary complex with acid-labile subunit (ALS), significantly prolonging the half-life of the circulating IGF1-IGFBP binary complex [16].