COX8A encodes cytochrome c oxidase subunit 8A, the smallest nuclear-encoded structural subunit of cytochrome c oxidase (complex IV), which is essential for mitochondrial oxidative phosphorylation 1. COX8A is required for the structural stability of complex IV monomers and dimers, with its loss resulting in 20-30% residual enzymatic activity and rapid degradation of unstable monomers while preserving supercomplexes with complexes I and III 2. Mutations in COX8A cause severe mitochondrial disease, including Leigh-like syndrome with leukodystrophy and epilepsy, demonstrating its indispensable role in human complex IV function 1. The protein serves as a biomarker for mitochondrial dysfunction in various pathological conditions, including sepsis where COX8A downregulation accompanies metabolic dysregulation 3, and cancer where it acts as a downstream target mediating oncogenic effects through mitochondrial respiratory function regulation 4. COX8A has been utilized as a mitochondrial marker for studying cristae dynamics using super-resolution microscopy, enabling visualization of mitochondrial inner membrane architecture in living cells 5. The gene's expression is also identified as a potential therapeutic target in drug resistance prediction models across different cancer types 6.