Therefore, one of the features of impaired MNs in ALS patients is that Ca2+ homeostasis is disturbed [105], which has been simulated using in vitro or in vivo models with mutated genes such as SOD1 [106], TDP-43 [107], FUS, etc. In mitochondria, one of the main functions of the endoplasmic reticulum (ER) is to regulate the uptake of Ca2+, especially to promote Ca2+ exchange with mitochondria after the release of Ca2+ stored in ER, but TDP-43 disrupts the ER/mitochondria association, reducing mitochondrial Ca levels [108]. Here, TARDBP is linked to amyotrophic lateral sclerosis.