ND3 (mitochondrially encoded NADH dehydrogenase 3) is a core subunit of mitochondrial respiratory Complex I that catalyzes electron transfer from NADH through the respiratory chain using ubiquinone as an electron acceptor, and is essential for Complex I catalytic activity 1. The gene encodes a mitochondria-transcribed mRNA that can be targeted by disease-associated proteins like TDP-43, which binds ND3 mRNA and impairs its expression, leading to Complex I disassembly and mitochondrial dysfunction in neurodegenerative diseases 2. ND3 variants cause severe mitochondrial disorders including Leigh syndrome and Leber hereditary optic neuropathy, with mutations like m.10197G>C significantly reducing MT-ND3 protein levels, Complex I assembly and activity, and ATP synthesis 3. The m.10197G>A mutation shows age-dependent phenotypic presentation, with earlier onset correlating with Leigh syndrome and later onset with optic neuropathy 4. ND3 expression levels show sexual dimorphism in human spinal cord oligodendrocytes, being higher in females than males 5. Therapeutic approaches include allotopic expression of codon-optimized ND3 that can partially restore protein levels and ATP production in patient cells 3.