Of note, ALS patients are subject to numerous other forms of stress in addition to that caused by energy imbalance (Masrori and Van Damme, 2020), and therefore, the potential contributions of the other three stress-sensing ISR kinases (i.e., PERK, PKR, and HRI) should also be considered. Here, EIF2AK3 is linked to amyotrophic lateral sclerosis.