Nr2e3 could activate the expression of ESR1 through binding to the promoter region of ESR1, and upregulation of Nr2e3 is related to recurrence‐free survival of ESR1‐positive breast cancer after tamoxifen treatment.[30] Meanwhile, Nr2e3 also promotes the metastasis of ESR1‐negative breast cancer through upregulation of the expression of IL13α2.[31] In addition, Nr2e3 reduction is also involved in the poor prognosis of liver cancer.[32] However, whether Nr2e3 is expressed in the central nervous system and involved in the epigenetic mechanism of depression is unknown. This evidence concerns the gene ESR1 and depressive disorder.