Also, PERK contributes to the development of renal fibrosis induced by trimethylamine N-oxide, a gut metabolite implicated in CKD, associated with the Akt/mTOR pathway and NLRP3 and Cas-1 activation (Shu et al. 2021; Kapetanaki et al. 2021). On the other hand, the inhibition of PERK suppresses fibrosis in a model of tunicamycin-induced CKD, a classical ER stress inducer (Shu et al. 2021). This evidence concerns the gene EIF2AK3 and chronic kidney disease.