DERL1 (derlin 1) is an endoplasmic reticulum (ER) membrane protein that functions as a critical regulator of protein quality control and cellular homeostasis. Structurally, DERL1 localizes to ER and lysosomal membranes 1 and participates in ER-associated degradation (ERAD) pathways 2, facilitating retrograde transport and ubiquitin-mediated degradation of misfolded proteins. DERL1 interacts with VCP (valosin-containing protein) and autophagy machinery to regulate protein stability and degradation dynamics 1. Beyond normal physiology, DERL1 demonstrates significant disease relevance in multiple malignancies. DERL1 is upregulated in triple-negative breast cancer, uveal melanoma, non-small-cell lung cancer, and thyroid cancer, where it promotes cell proliferation, migration, invasion, and chemoresistance 345. In oral squamous cell carcinoma, elevated DERL1 mediates cisplatin resistance in mesenchymal-like cells 6. DERL1 is also downregulated in polycystic ovary syndrome granulosa cells 7 and involved in recurrent pregnancy loss through endoplasmic reticulum stress pathways 8. Clinically, DERL1 represents a therapeutic target—VCP inhibitors and DERL1 knockdown reduce cancer progression, while miR-575 and melatonin-mediated DERL1 suppression enhances chemosensitivity 165.