Similarly, the Sigma-1 receptor (S1R) is a multi-functional, ligand-operated protein situated at MAM site which has also been associated with various neurological disorders, including amyotrophic lateral sclerosis/frontotemporal dementia, and Alzheimer’s (AD) and Huntington’s diseases (HD) [84,85,86]. This evidence concerns the gene TMBIM4 and amyotrophic lateral sclerosis.