In ALS/FTD, overexpression of both wild-type and familial ALS/FTD mutant TDP-43 has been shown to not only reduce ER–mitochondria associations, but also disrupt Ca2+ exchange between the two organelles, which is a physiological readout of ER–mitochondria contacts [32]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.