This review summarizes the current knowledge regarding the functions of PGC-1α in the brain and its role in neurological diseases, such as intracerebral hemorrhage (ICH), ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), and Polyglutamine (PolyQ) diseases. Here, PPARGC1A is linked to amyotrophic lateral sclerosis.