Plays a role in protein homeostasis by regulating both the translocation and the ubiquitin-mediated proteasomal degradation of nascent proteins at the endoplasmic reticulum (PubMed:24160817, PubMed:26337389, PubMed:26692333). It is involved in the regulation of signal-mediated translocation of proteins into the endoplasmic reticulum (PubMed:24160817). It also plays a role in the ubiquitin-mediated proteasomal degradation of proteins for which signal-mediated translocation to the endoplasmic reticulum has failed (PubMed:18467495, PubMed:26337389). May therefore function in the 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:24160817, PubMed:26337389). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333). Binds 'Lys-48'-linked polyubiquitin chains of ubiquitinated proteins (PubMed:18467495, PubMed:24160817, PubMed:26876100). Associates with the proteasome complex; upon exposure to arsenite (PubMed:18467495, PubMed:26876100). Interacts (via VIM motif) with VCP; the interaction is direct (PubMed:24160817, PubMed:26337389). Interacts with BAG6 (PubMed:24160817, PubMed:26337389, PubMed:26876100). Interacts with IGF1R (nascent precursor form) (PubMed:26692333). Interacts with DERL1, FAF2, NPLOC4 and UFD1; probably through VCP (PubMed:24160817). The UIM domains specifically bind 'Lys-48'-linked ubiquitin polymers (PubMed:18467495, PubMed:26876100). The UIM domains mediate interaction with polyubiquitinated proteins (PubMed:18467495, PubMed:26337389). Phosphorylated by MAPK14 (Probable). Phosphorylation has no effect on association with the proteasome complex (Probable). Knockout mice undergo premature death due to the occurrence of myelo-proliferative neoplasms. The absence of Zfand2b plays a driver role in the development of these neoplasms by hyperactivating the insulin-like growth factor receptor signaling pathway. This is due to increased expression, in particular at the cell surface, of the IGF1R receptor.