IGFBP3 and amyotrophic lateral sclerosis: Most of the serum-circulating IGF-1 (approximately 80%) is included in this complex (Figure 1), which increases the serum IGF-1 half-life.1 In fact, biallelic loss-of-function mutations in IGFALS result in severe reduction in levels of circulating functional ALS and the inability to produce a ternary complex, with consequently lower IGF-1 and IGFBP-3 levels.