Here, inspired by our identification of a rare polymorphism in the SNCG gene of two individuals with ALS in the absence of mutations in the SOD1, TDP-43, C9orf72, FUS, and ANG genes commonly associated with ALS, we explored the role of the identified sequence change (Met38 for Ile), which lies within in the P1 region of γSyn, in modulating its ability to form amyloid fibrils in vitro, in cells and in fly models. Here, C9orf72 is linked to amyotrophic lateral sclerosis.