Derlin-2 (DERL2)

Derlin-2 is an integral membrane protein of the endoplasmic reticulum (ER) that is central to the ER-associated degradation (ERAD) pathway, where it mediates the recognition and retrotranslocation of misfolded glycoproteins from the ER lumen to the cytosol for ubiquitin-proteasome-dependent degradation[1][4]. Derlin-2 forms part of a dislocation complex that includes proteins like Sel1L, VIMP, p97, HRD-1, OS-9, and Ubc6e[2]. Its function is essential for the removal of certain misfolded substrates, maintaining ER proteostasis and preventing activation of stress pathways such as the unfolded protein response (UPR)[2]. Derlin-2-deficient cells and tissues upregulate components of both the ERAD machinery and UPR signaling; in mice, whole-body deletion leads to perinatal lethality, and survivors exhibit skeletal abnormalities due to impaired secretion of collagen matrix proteins from chondrocytes[2]. Its primary molecular role is not as a traditional "drug target", but as a crucial component for intracellular protein homeostasis and the prevention of diseases linked to protein misfolding and aggregation[1][2][4].

Other names

Derlin-2DERL2DER2FLANACGI-101SBBI53DERtrin-2F-LAN-1F-LANaderlin-2Degradation in endoplasmic reticulum protein 2Der1-like protein 2Der1-like domain family member 2, carcinoma relateddegradation in endoplasmic reticulum protein 2