Up to now, within the CNS, three different isoforms, NCX1, NCX2 and, NCX3, and numerous splicing variants have been identified; the precise involvement of each NCX isoform in ALS progression and etiology has not yet been determined, nonetheless some seminal works postulated a crucial role for NCX3 in mediating the impairment in neuromuscular transmission occurring ALS and in other related disease (Sokolow et al., 2004; Boscia et al., 2012; Casamassa et al., 2016; Anzilotti et al., 2018), thus rendering it a putative druggable target in ALS. Here, TLX2 is linked to amyotrophic lateral sclerosis.