In the course of evolution, the most highly developed organ is likely the brain, which has become more complex over time and acquired diverse forms and functions in different species. In particular, mammals have developed complex and high-functioning brains, and it has been reported that several genes derived from retroviruses were involved in mammalian brain evolution, that is, generating the complexity of the nervous system. Especially, the sushi-ichi-related retrotransposon homolog (SIRH)/retrotransposon gag-like (RTL) genes have been suggested to play a role in the evolutionary processes shaping brain morphology and function in mammals. Genetic mutation and altered expression of genes are linked to neurological disorders, highlighting how the acquisition of virus-derived genes in mammals has both driven brain evolution and imposed a susceptibility to diseases. This review provides an overview of the functions, diversity, evolution and diseases associated with SIRH/RTL genes in the nervous system. The contribution of retroviruses to brain evolution is an important research topic in evolutionary biology and neuroscience, and further insights are expected to be gained through future studies.