RTN4IP1 encodes a mitochondrial NAD(P)H oxidoreductase with dual critical functions in cellular metabolism and disease pathogenesis. **Primary Function and Mechanism:** RTN4IP1 serves as a NAD(P)H oxidoreductase involved in ubiquinone biosynthesis 1, catalyzing oxidoreduction of ubiquinone intermediates. More importantly, RTN4IP1 functions as a bona fide complex I assembly factor required for terminal stages of mitochondrial complex I assembly 23. Complexome profiling reveals it facilitates ND5-module incorporation and N-module production 2. **Disease Relevance:** RTN4IP1 mutations cause autosomal recessive optic neuropathies, ranking among the top 10 genes in hereditary optic neuropathies 45. Patient fibroblasts with RTN4IP1 mutations exhibit complex I and IV deficiency and increased UV sensitivity 5. The gene also contributes to esophageal squamous cell carcinoma (ESCC) progression through regulation of amino acid transporters SLC1A5, SLC3A2, and SLC7A5 6. **Clinical Significance:** RTN4IP1 overexpression predicts adverse prognosis in breast cancer 7, while paradoxically acting as a tumor suppressor in thyroid cancer 8. This context-dependent role suggests RTN4IP1 functions as a critical metabolic hub linking mitochondrial bioenergetics to cancer progression and neurodegeneration.