Sigma-1 receptor (S1R) is a multi-functional, ligand-operated protein situated in endoplasmic reticulum (ER) membranes and changes in its function and/or expression have been associated with various neurological disorders including amyotrophic lateral sclerosis/frontotemporal dementia, Alzheimer’s (AD) and Huntington’s diseases (HD). Here, TMBIM4 is linked to Alzheimer disease.