Although studies emphasized the role of the GluN2A and AKT signaling cascade in LPS-induced depression (Francija et al., 2018; Li et al., 2018), it remains open how Ephrin receptor signaling acts on NMDARs and AKT signaling contributes to decreased neuroplasticity and aberrant behavior upon LPS treatment. The gene discussed is GRIN2A; the disease is major depressive disorder.