PSEN1 and familial Alzheimer disease: No. A recent work by Tong et al. (2022) [46] claimed that exaggeration of TPC2 activity in SH-SY5Y neuroblastoma cells expressing mutant Presenilin 1 (PSEN1) and human fibroblasts from familial Alzheimer’s disease patients results in the reduction of lysosomal Ca2+, which in turn accelerates the Ca2+/H+ exchanger to expel H+ leading to lysosomal alkalinization and reduction in autophagy clearance of amyloids.