TARDBP and amyotrophic lateral sclerosis: Indeed, cell-autonomous effect of loss of CLCC1 function on motor neuron loss and ubiquitin-positive and mislocalized TDP-43 (Fig. 6) links CLCC1 dysfunction to common ALS pathologies and its underlying disease mechanisms.42,63,64 Dysfunction of RNA binding proteins (RBPs), including TDP-43, often leads to stress granule processing.43,44 It will be intriguing to further investigate the crosstalk between ER and membraneless organelles, like stress granule,65 and how dysfunctions in two cellular systems converge with the pathogenesis of ALS.