IGF1 and amyotrophic lateral sclerosis: In addition, considering that the main effect on IGF release was the proteolysis of IGFBP [36] and that it has been demonstrated in an ALS knockout mouse model that ALS plays a critical role in regulating circulating levels of these proteins [37, 45], we hypothesized that ALS mainly plays a role in biological function by influencing the formation of the IGF-IGFBP-ALS complex.