NDUFS1 is a core subunit of mitochondrial respiratory chain Complex I that catalyzes electron transfer from NADH to ubiquinone 12. It is essential for efficient electron entry and transfer within Complex I and plays a critical role in assembly and stability of the complex, participating in supercomplex formation with Complex III 2. NDUFS1 expression is dynamically regulated during cellular processes; it is upregulated in MI-stage oocytes during maturation 3 and its acetylation status is modulated by SIRT3 to regulate mitochondrial oxidative phosphorylation 4. In cancer biology, NDUFS1 has contrasting roles: PHB2-mediated stabilization of NDUFS1 enhances Complex I activity and promotes colorectal cancer proliferation 5, while NDUFS1 downregulation in gastric cancer activates mitochondrial ROS-HIF1α signaling, also promoting tumorigenesis 6. In the cardiovascular system, βII spectrin facilitates NDUFS1 translocation to mitochondria, maintaining Complex I activity and cardiac function 7. NDUFS1 dysfunction contributes to multiple pathologies: genetic variants associate with schizophrenia risk and negative symptom severity 8, while F-53B-induced NDUFS1 downregulation impairs mitochondrial respiration in neuronal cells 9. NDUFS1 has been identified as a disulfidptosis-related gene in Parkinson's disease pathogenesis involving oxidative stress 10. These findings establish NDUFS1 as a central regulator of cellular bioenergetics with implications for metabolic disorders and neurodegeneration.