The negative effects of loss of GBA2 function in HSP, ARCA, and Marinesco-Sjögren-like syndrome, but positive effects of GBA2 inhibition in Gaucher, Niemann-Pick and ALS models, suggests that GBA2 is part of an important fine-tuning mechanism in lipid metabolism that is particularly critical in neuronal cells. This evidence concerns the gene GBA2 and amyotrophic lateral sclerosis.