Sigma-2 receptors have been studied for more than four decades and are drug targets for several conditions including cancer, pain and diverse CNS disorders [22, 58]; and most notably, a Sigma-2 modulator, CT1812, is in clinical development in Phase 2 trials for Alzheimer’s disease and dementia with Lewy bodies [11, 21]. The gene discussed is TMEM97; the disease is early-onset autosomal dominant Alzheimer disease.