2011). In our results, we show a direct interaction between the Sig‐1R and Kv1.2 under control conditions and that ligand activation of the Sig‐1R inhibits Kv1.2 channel current. Moreover, simply increasing expression levels of the Sig‐1R leads to a change in the activation gating state of Kv1.2, from predominantly “fast” to predominantly “slow.” These effects are not observed in the presence of Sig‐1R‐E102Q, suggesting that aberrant Kv1.2 channel modulation may underlie neuronal hyperexcitability observed in ALS (Do‐Ha et al. 2018; Fogarty 2018). Here, SIGMAR1 is linked to amyotrophic lateral sclerosis.