There is evidence that VAPB and PTPIP51 protein levels are reduced in disease; lower levels of both VAPB and PTPIP51 are seen in an affected region of post-mortem Alzheimer’s disease brains (temporal cortex) and lower levels of VAPB are seen in ALS spinal cord [1, 39, 58]. Here, RMDN3 is linked to early-onset autosomal dominant Alzheimer disease.