FAD-dependent oxidoreductase domain containing 2 (FOXRED2)

FAD-dependent oxidoreductase domain containing 2 (FOXRED2) is an endoplasmic reticulum-localized flavoprotein enzyme that functions in ER-associated degradation (ERAD), binding and possibly helping to process misfolded or non-native proteins for ubiquitin-mediated degradation[3][4]. FOXRED2 modulates proteostasis by influencing proteasome assembly and activity; for example, its upregulation by amyloid β results in inhibition of proteasome function, triggering ER stress and caspase-12-mediated apoptosis—a mechanism implicated in neurodegeneration[2]. In cancer cells, FOXRED2 can activate hypoxia-targeted prodrugs, thereby serving as a biomarker and potential therapeutic target to enhance cytotoxic efficacy under low-oxygen conditions[1]. It is also part of transcriptomic signatures relevant for prognosis in KRAS-driven non-small cell lung cancer[1]. Although not currently associated with widely-approved drugs beyond experimental contexts, its dual involvement in cell death pathways and hypoxia drug activation highlight its emerging importance in both cancer and neurodegenerative disease research[3][2][1].

Other names

FOXRED2ERFADFAD-dependent oxidoreductase domain-containing protein 2ER flavoprotein associated with degradationEndoplasmic reticulum flavoprotein associated with degradationFLJ23322

Reductive activation of nitro-chloromethylbenzindolines and other hypoxia-targeting prodrugs, increasing cytotoxic efficacy under hypoxic conditions[1]; Modulation of cell death via ER stress induction and proteasome inhibition (seen in amyloid β-induced neurotoxicity)[2]