UQCRFS1 (ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1) is a critical component of mitochondrial complex III, the ubiquinol-cytochrome c oxidoreductase complex involved in oxidative phosphorylation and cellular respiration 1. Located on chromosome 19, UQCRFS1 undergoes proteolytic processing after incorporation into the complex III dimer, which is essential for proper assembly and function of the respiratory chain 1. In microglia, mitochondrial respiration via complex III is dispensable for cell proliferation but essential for appropriate responses to demyelinating CNS injury 2. Beyond its canonical metabolic role, UQCRFS1 has emerged as a significant oncogenic factor. High UQCRFS1 expression correlates with poor prognosis in triple-negative breast cancer, ovarian cancer, and diffuse large B-cell lymphoma, where it promotes tumor progression through enhanced proliferation and reduced apoptosis 34. In lymphomas, UQCRFS1-marked high oxidative phosphorylation activity is associated with CD8+ T cell exhaustion and immune checkpoint blockade resistance 5. UQCRFS1 gene amplification occurs in approximately 13% of breast and ovarian cancer samples and associates with aggressive cancer phenotypes 67. Additionally, UQCRFS1 is identified as a hub biomarker in Alzheimer's disease progression 8. Germline mutations in UQCRFS1 cause mitochondrial complex III deficiency, a nuclear-encoded mitochondrial disorder affecting energy metabolism.