CHCHD2 (coiled-coil-helix-coiled-coil-helix domain containing 2) is a mitochondrial protein with dual roles as a transcription factor and regulator of mitochondrial dynamics. As a transcription factor, CHCHD2 binds to oxygen-responsive elements and activates transcription under both hypoxic and normoxic conditions 1. The protein localizes to mitochondrial intermembrane space and nucleus, where it regulates mitochondrial ATP synthesis and cellular responses to oxidative stress 1. CHCHD2 functions as a mitochondrial integrated stress response (mtISR) suppressor by interacting with OMA1 to restrain stress responses and suppress OPA1 processing for mitochondrial fusion 2. During mitochondrial stress, CHCHD2 translocates to the cytosol and interacts with eIF2α to attenuate mtISR overactivation 2. Disease-associated mutations in CHCHD2 cause autosomal dominant Parkinson's disease through loss-of-function mechanisms 34. Protein-truncating variants, particularly p.P53Afs*38 found exclusively in Asian populations, are enriched in early-onset Parkinson's disease and cause mitochondrial dysfunction 3. CHCHD2 dysregulation is also implicated in Huntington's disease neurodevelopment, where mutant huntingtin disrupts CHCHD2-mediated neurometabolic programming 5. Beyond neurological diseases, CHCHD2 overexpression promotes liver fibrosis in nonalcoholic steatohepatitis through Notch/osteopontin signaling 6.