In light of the central role Ranbp2 plays in controlling the Ran GTPase cycle (Patil et al., 2014; Cho et al., 2010; Villa Braslavsky et al., 2000; Vetter et al., 1999; Hamada et al., 2011; Ritterhoff et al., 2016) and the nucleocytoplasmic shuttling and proteostasis of ALS-causing substrates [i.e. hnRNPA2B1 (Kim et al., 2013; Cho et al., 2015b, 2014)], we hypothesized that Ranbp2 plays an instrumental role in motoneuron biology and disease, and tested this idea by producing mouse models lacking Ranbp2 in Thy1 motoneurons of the anterior horns of the spinal cord. Here, RANBP2 is linked to amyotrophic lateral sclerosis.