PERK inhibition in hearts: angel or devil?

In their recent opinion article in Trends in Molecular Medicine entitled ‘Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias’ [ 1. Liu M. et al. Preventing unfolded protein response-induced ion channel dysregulation to treat arrhythmias. Trends Mol. Med. 2022; 28: 443-451 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar ], Liu et al. proposed that unfolded protein response (UPR) contributes to ion channel downregulation and arrhythmic risk in cardiomyopathy. They also mentioned that among the three independent arms of UPR, only the protein kinase RNA-like ER kinase (PERK) arm activation has been found consistently harmful. Thus, the authors summarized that PERK inhibition in cardiomyopathy may represent a novel antiarrhythmic strategy.