Epigenetic regulation plays critical roles in the development and homeostasis of the nervous system. Protein arginine methylation is a post-translational modification commonly found in nearly all eukaryotic cells, which regulates a variety of physiological events, such as gene transcription regulation or RNA splicing, via mediating the methylation of histone or nonhistone targets. This review aims to recapitulate the regulatory mechanism underlying protein arginine methyltransferase 5 (PRMT5) function, and summarize the crucial roles of PRMT5 in neural development and neurological diseases, highlighting its epigenetic regulatory mechanism in the nervous system.