NDOR1 (NADPH-dependent diflavin oxidoreductase 1) is a cytosolic reductase that plays a central role in iron-sulfur (Fe-S) cluster assembly and maintenance. As a key component of the cytosolic iron-sulfur protein assembly (CIA) machinery, NDOR1 transfers electrons from NADPH through its FAD and FMN prosthetic groups to the [2Fe-2S] cluster of CIAPIN1 (anamorsin) 12. This electron transfer activates CIAPIN1 to facilitate assembly of cytosolic and nuclear Fe-S cluster proteins, which are essential for ribosome maturation, transcription, and DNA repair 1. Beyond Fe-S assembly, NDOR1 also reduces the [2Fe-2S] cluster of CISD1/mitoNEET, enabling Fe-S cluster repair of iron regulatory protein 1 (IRP1) under oxidative stress conditions 3. Functionally impaired NDOR1 variants exist naturally; the NDOR1*1 polymorphism (c.1564G>A) produces a 74-90% reduction in reductase activity, potentially affecting cellular iron homeostasis 4. Clinically, elevated NDOR1 expression associates with poor prognosis in hepatocellular carcinoma, suggesting involvement in cancer progression 5. This multifaceted oxidoreductase is thus critical for cellular Fe-S protein biogenesis, iron homeostasis, and stress response mechanisms.