CHCHD6 is a core component of the mitochondrial contact site and cristae organizing system (MICOS) complex, a large protein assembly of the inner mitochondrial membrane essential for maintaining cristae structure and mitochondrial architecture 12. CHCHD6 physically interacts with other MICOS components including mitofilin, CHCHD3, and Sam50 to sustain cristae morphology and organization 12. Loss of CHCHD6 results in reduced cristae density, impaired mitochondrial morphology, and decreased ATP production and oxygen consumption 2. CHCHD6 dysfunction contributes to age-related mitochondrial deterioration in skeletal and cardiac muscle, with reduced MICOS complex expression correlating with sarcopenia and cardiac aging phenotypes 34. In Alzheimer's disease, CHCHD6 plays a critical mechanistic role connecting amyloid-beta pathology to mitochondrial dysfunction through a feedback loop where APP intracellular domain fragments suppress CHCHD6 transcription, reducing CHCHD6 levels and promoting APP accumulation and neuronal damage 5. Additionally, CHCHD6 variants are associated with mitochondrial dysfunction in non-alcoholic fatty liver disease and glaucoma medication non-adherence, highlighting its broader metabolic significance 67. These findings position CHCHD6 as a therapeutic target for age-related diseases and neurodegenerative conditions.