Herein, we will discuss in detail the available evidence of the physiological role of CHIP in the context of neurological diseases, such as intracerebral hemorrhage (ICH), ischemic stroke, Alzheimer’s disease (AD), Parkinson’s disease (PD), polyglutamine (PolyQ) diseases, and spinocerebellar ataxia autosomal recessive 16 (SCAR16) and spinocerebellar ataxia 48 (SCA48) caused by CHIP mutation (Fig. 1). This evidence concerns the gene STUB1 and autosomal recessive spinocerebellar ataxia 16.