CHCHD10 encodes a mitochondrial intermembrane space protein that plays critical roles in maintaining mitochondrial structure and function 1. The protein regulates mitochondrial dynamics by interacting with OMA1 to suppress its enzyme activity, thereby controlling OPA1 processing for mitochondrial fusion and restraining mitochondrial integrated stress response (mtISR) initiation 1. CHCHD10 also interacts with Stomatin-Like Protein 2 (SLP2) to maintain stability of the prohibitin complex in the inner mitochondrial membrane, which is essential for proper mitochondrial cristae organization 2. Dominant mutations in CHCHD10 cause a spectrum of neurodegenerative and neuromuscular disorders through gain-of-function mechanisms involving protein misfolding into toxic species 3. Disease-associated variants include p.R15L and p.S59L causing amyotrophic lateral sclerosis and frontotemporal dementia, p.G66V causing Spinal Muscular Atrophy Jokela type, and p.G58R causing isolated mitochondrial myopathy 34. Pathogenic mutations lead to prohibitin complex destabilization, OMA1 cascade activation, mitochondrial fragmentation, and abnormal cristae morphogenesis, ultimately resulting in motor neuron death 2. The severity of motor neuron disease correlates with mutant protein dosage, with altered energy metabolism and creatine metabolism disruption contributing to pathogenesis 4.