We recently found that 10.5% of sporadic Parkinson’s disease (PD) patients lacked one copy of the midnolin ( MIDN ) gene. In addition, gene knock-down/out of MIDN caused down-regulation of parkin E3 ubiquitin ligase, indicating MIDN to be a novel PD-risk factor or causative gene. In this study, we performed RNA-sequencing and transcriptome analysis of Midn wild-type and knockout cells. Midn positively or negatively regulated the expression of a wide variety of genes, including causative familial PD genes, such as α-synuclein, parkin, and EIF4G1. However, EIF4G1 protein levels were not altered by the reduction of its mRNA by Midn loss, as seen that parkin protein levels were correlated to the mRNA down-regulation. Taken together, these findings indicate that MIDN regulates the expression of a wide variety of genes, including multiple PD-causative genes and is associated with PD onset.