BOLA3 (bolA family member 3) is a mitochondrial iron-sulfur (Fe-S) cluster assembly factor that facilitates the insertion of Fe-S clusters into mitochondrial proteins 1. BOLA3 functions as a [2Fe-2S] cluster-binding protein that forms heteromeric complexes with glutaredoxin GRX5 and works alongside NFU1 to deliver [4Fe-4S] clusters to specific substrates 23. The protein plays a critical role in incorporating Fe-S clusters into mitochondrial respiratory chain complexes I and II, lipoic acid synthetase, and the mitoribosome 43. Pathogenic BOLA3 variants cause Multiple Mitochondrial Dysfunctions Syndrome 2 with hyperglycinemia (MMDS2), characterized by life-threatening lactic acidosis, nonketotic hyperglycinemia, and hypertrophic cardiomyopathy 4. Disease manifestations result from impaired Fe-S cluster delivery to respiratory complexes and lipoic acid-dependent enzymes, causing metabolic disruption and reduced mitochondrial protein synthesis 43. Beyond primary mitochondrial disease, BOLA3 expression associates with beige adipocyte thermogenesis and immune-related prognosis in lung adenocarcinoma 56. Therapeutically, targeting the Fe-S cluster assembly pathway rather than downstream metabolic effects may provide more effective treatment for BOLA3 deficiency 4.