COA4 (cytochrome c oxidase assembly factor 4 homolog) is a mitochondrial protein localized to the intermembrane space that functions as a critical assembly factor for cytochrome c oxidase (COX), a multimeric copper-containing enzyme essential for cellular respiration 1. COA4 contains a conserved twin CX9C motif and plays a key role in the mitochondrial copper delivery pathway, particularly for copper site biogenesis in the Cox1 subunit 12. Mechanistically, COA4 functions through dual pathways: mitochondrial COA4 augments COX activity to enhance oxidative phosphorylation, while cytosolic COA4 binds and activates CDC42 to regulate pseudopodia formation and cell migration 3. These functions are evolutionarily conserved, as the yeast ortholog Coa4 can be functionally replaced by human COA4 1. COA4 is highly overexpressed in KRAS mutant tumors, where it drives cancer metastasis through COX-dependent and CDC42-dependent mechanisms independent of tumor proliferation 3. Additionally, COA4 participates in ferroptosis regulation through the SIRT6/COA4/FTH1 pathway, protecting cells from oxidative stress-induced ferroptotic death 4. COA4 is identified as a cancer-promoting protein whose downregulation correlates with reduced metastatic potential 5, establishing it as a therapeutic target in KRAS-driven malignancies.