This cluster of papers focuses on the molecular mechanisms, regulation, and consequences of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). It explores the role of ER stress in various diseases such as diabetes, cancer, neurodegenerative diseases, and liver disease, highlighting its impact on cell fate decisions, protein folding, oxidative stress, and apoptosis. The cluster also delves into the involvement of UPR pathways, chaperones, and the interplay between ER stress and inflammation.