COX7A2L is a mitochondrial assembly factor that mediates the formation of respiratory supercomplexes, particularly the CIII₂IV₂ supercomplex and larger structures like the CS-respirasome (MCI₁III₂IV₂) 12. It functions as a molecular adapter associating with both respiratory complexes III and IV to promote their functional organization 3. COX7A2L plays a critical regulatory role in metabolic adaptation: supercomplexes assembled by COX7A2L maintain oxidative phosphorylation under low-oxygen conditions and facilitate metabolic rewiring toward glycolysis 3. The protein is essential for preventing metabolic exhaustion through coordinated MRC organization 3. Under nutrient and ER stress, PERK-eIF2α signaling upregulates COX7A2L to enhance supercomplex assembly and ATP production 4. Genetically, COX7A2L variants in the 3' UTR affect muscle expression levels, with increased expression correlating with higher cardiorespiratory fitness, greater lean mass, and reduced body fat in humans 5. In metabolic disease contexts, COX7A2L knockdown promotes glutaminolysis and cell proliferation while enhancing antioxidative defense 6. Clinical evidence suggests COX7A2L may modulate apoptosis and proliferation in acute kidney injury through Wnt/β-catenin pathway regulation 7. However, recent cardiomyocyte studies suggest COX7A2L's effects on cell viability may be cell-type specific 8.