ERN1 and amyotrophic lateral sclerosis: Interestingly, Lee et al. (2016) identified that homeodomain-interacting protein kinase 2 (HIPK2) is involved in ER-stress-mediated activation of IRE1 in multiple ALS models, including both the SOD1 and TDP-43 transgenic mouse models, as well as sALS and C9orf72-related ALS patient postmortem tissues [50].