COX5A encodes a nuclear-encoded subunit of cytochrome c oxidase (Complex IV), the terminal enzyme of the mitochondrial respiratory chain that catalyzes oxygen reduction to water during oxidative phosphorylation 1. COX5A plays a crucial role in maintaining mitochondrial respiratory function, ATP synthesis, and cellular energy metabolism 2. The protein helps regulate complex IV activity and oxygen consumption rates while modulating reactive oxygen species production 13. COX5A demonstrates significant clinical relevance across multiple pathological contexts. In cardiovascular disease, COX5A overexpression protects against doxorubicin-induced cardiotoxicity by suppressing oxidative stress, preserving mitochondrial function, and preventing cardiomyocyte apoptosis through PI3K/Akt signaling pathways 23. The protein also protects vascular smooth muscle cells against phenotypic modulation and neointima formation 1. In neurodegeneration, COX5A overexpression improves spatial memory and hippocampal synaptic plasticity in aging models through BDNF/ERK1/2 signaling 4. Additionally, COX5A serves as a potential biomarker for disease activity and organ damage in systemic lupus erythematosus 5 and is associated with poor prognosis in estrogen receptor-positive breast cancer, where it promotes invasion and chemoresistance 6. These findings establish COX5A as a critical regulator of mitochondrial function with therapeutic potential across multiple diseases.