NUBPL is a mitochondrial iron-sulfur cluster assembly factor essential for Complex I biogenesis. It functions as an iron-sulfur cluster transfer protein that delivers Fe-S clusters to NADH dehydrogenase (Complex I) subunits 1, playing a critical role in assembling the mitochondrial respiratory chain. Pathogenic NUBPL variants cause mitochondrial complex I deficiency with autosomal recessive inheritance 2. Clinically, NUBPL-related leukodystrophy typically presents in infancy (3-18 months) with developmental delay, cerebellar dysfunction (ataxia, dysarthria, nystagmus), spasticity, and progressive neurological decline 3. Brain MRI characteristically shows white matter abnormalities with cerebellar atrophy, particularly T2 hyperintensity of cerebellar cortex 45. Patient fibroblasts demonstrate significantly reduced mitochondrial spare respiratory capacity 3. The phenotypic spectrum has expanded beyond the original presentation, with variable disease severity, earlier onsets, and occasional extraneurological involvement including white matter cystic degeneration and involvement of thalami and basal ganglia 5. Beyond primary mitochondrial function, emerging evidence suggests NUBPL may have broader roles in cellular biology, including associations with disulfidptosis-related pathways and cancer progression 67, though its pathogenic significance in these contexts remains clarification.