Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins (PubMed:15215856, PubMed:33658201). Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane (PubMed:33658201). This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome (PubMed:33658201). The channel has a lateral gate within the membrane which provides direct access to membrane proteins with no need to reenter the ER lumen first (PubMed:33658201). May mediate the interaction between VCP and the misfolded protein (PubMed:15215856). Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). (Microbial infection) In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein. Homotetramer (PubMed:33658201). The four subunits of the tetramer are arranged in a twofold symmetry (PubMed:33658201). Forms heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts (via SHP-box motif) with VCP (PubMed:16289116, PubMed:16186510, PubMed:16186509, PubMed:16449189, PubMed:27714797). Interacts with AMFR, SELENOS, SEL1L, SELENOK and SYVN1, as well as with SEL1L-SYVN1 and VCP-SELENOS protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with DNAJB9. Interacts with RNF103 (PubMed:15215856, PubMed:16055502, PubMed:16186509, PubMed:16186510, PubMed:16289116, PubMed:16449189, PubMed:18675248, PubMed:19818707, PubMed:22016385). Interacts with HM13 (PubMed:25239945). Interacts with XBP1 isoform 1 (via luminal/ectodomain domain); the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage (PubMed:25239945). Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (PubMed:26565908). May interact with UBXN6 (PubMed:19275885). Interacts with ZFAND2B; probably through VCP (PubMed:24160817). Interacts with CCDC47 (By similarity). Interacts with C18orf32 (PubMed:29275994). May interact with TRAM1 (PubMed:19121997). (Microbial infection) Interacts with the cytomegalovirus US11 protein. Ubiquitous. Belongs to the derlin family.