Edem1, also known as endoplasmic reticulum degradation-enhancing α -mannosidase-like protein 1, is a key quality control factor directly involved in the endoplasmic reticulum-associated degradation (ERAD) process. It recognizes terminally misfolded proteins in the endoplasmic reticulum (ER) and guides them to retrotranslocation followed by proteasomal degradation in the cytosol, thus maintaining ER homeostasis [1,3,6,7].

In human cell lines, overproduction of EDEM1 reduces amyloid-β precursor protein (APP) cellular levels and Aβ40 and Aβ42 secretion, while down-regulation of EDEM1 increases APP levels, indicating its role in APP metabolism through ERAD, which is relevant to Alzheimer's disease [1]. In INS-1E cells and human islets, EDEM1 overexpression inhibits the IRE1/JNK/c-Jun pathway, increasing insulin mRNA levels and insulin secretion. EDEM1 also improves insulin secretion in diabetic rats, suggesting its potential as a target for diabetes treatment [2]. In Drosophila, Edem1 in the fat body regulates insulin signalling and metabolic homeostasis by limiting the activity of Drosophila tumor necrosis factor-α Eiger on insulin-producing cells [5]. Additionally, EDEM1 itself is degraded by ERAD and autophagy, and its turnover is mediated by multiple degradation routes [3]. Alterations in EDEM1 functions can enhance ATF6 pro-survival signalling, and a somatic variant in hepatocellular carcinoma can affect ATF6 signalling [4].

In conclusion, Edem1 is crucial for maintaining ER homeostasis and has significant impacts on various biological processes and disease-related pathways. Its roles in APP metabolism related to Alzheimer's disease, insulin regulation relevant to diabetes, and metabolic homeostasis in Drosophila, as well as its own degradation regulation and influence on ATF6 signalling, highlight its importance in understanding disease mechanisms. The study of Edem1 using cell lines and animal models like Drosophila provides insights into these biological functions and disease associations.