With the aging population increasing worldwide, neurodegenerative diseases are becoming a major public health crisis. Neurodegenerative diseases are a group of neurologic disorders caused by the loss of the structure and function of neurons, mainly manifested by degenerative changes or death of neurons in specific regions. Neurodegenerative diseases are often classified into two categories: one affecting motor function, such as Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), and the other affecting cognitive function, such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Mitochondrial impairment manifesting in the affected neurons is a common feature in these neurodegenerative diseases. The coiled-coil-helix-coiled-coil-helix domain containing 10 (CHCHD10) is a mitochondrial protein encoded by the nuclear genome, mainly located in the mitochondrial intermembrane space. CHCHD10 plays a critical role in the maintenance of structural integrity and function of mitochondria. Various CHCHD10 gene mutations have been identified in different neurodegenerative diseases, including FTD, ALS, PD, AD, etc. Mutations of the CHCHD10 gene or loss of its function can lead to the loss of mitochondrial cristae structure and abnormal mitochondrial function. However, the specific function of the CHCHD10 protein and the mechanism underlying mitochondrial damage caused by its gene mutations remain unclear. Here we review the recent advances in the structure and mitochondrial function of CHCHD10 and discuss the mechanism of mitochondrial dysfunction induced by gene mutations or functional loss of CHCHD10. Investigating the role of CHCHD10 in maintaining mitochondrial function will help us to understand the pathological mechanism of neurodegenerative diseases and explore potential therapeutic interventions for these devastating diseases.