DERL3 (derlin 3) is a functional component of endoplasmic reticulum-associated degradation (ERAD) that selectively mediates retrotranslocation of misfolded lumenal glycoproteins into the cytosol for proteasomal degradation 1. The protein may form a channel facilitating glycoprotein extraction and mediate interactions between VCP and misfolded substrates. DERL3 also participates in ER stress-induced pre-emptive quality control, rerouting newly synthesized proteins to cytosolic degradation pathways. Clinically, DERL3 shows context-dependent roles in disease. In colorectal cancer, DERL3 acts as a tumor suppressor—low expression correlates with increased metastasis and poor prognosis, with DERL3 suppressing proliferation by negatively regulating MYCN 2. Conversely, in breast cancer and lung adenocarcinoma, elevated DERL3 associates with malignant phenotypes and shorter survival 34. In nasopharyngeal carcinoma, EBV-mediated DNA methylation silences DERL3, promoting tumor progression 5. DERL3 also contributes to rheumatoid arthritis pathogenesis through TNF-α-induced NF-κB activation in fibroblast-like synoviocytes 6. Recent evidence indicates altered DERL3 distribution in type 2 diabetes pancreatic β cells 7 and that post-translational succinylation regulates DERL3 stability during inflammatory responses 8. These findings suggest DERL3 represents a potential therapeutic target across multiple inflammatory and malignant diseases.