Previous studies demonstrated that Ephrin type-B receptor 2 (EPHB2) in the hypothalamus was significantly increased and interacted with the accumulated NMDAR subunit GluN2A in LPS-induced depressive phenotype mice (Wu et al., 2019), and the ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the PFC and HIP were increased in the social frustration depression mouse model (Zhang et al., 2017). Here, NGEF is linked to major depressive disorder.