By these multifaceted roles, NRGs/ErbB signaling controls key physiological neural functions, affecting learning and memory processes and complex behaviors, and its dysfunction is emerging as a pathological feature in different neurological and psychiatric disorders, including schizophrenia, bipolar disorder, autism spectrum disorders, Alzheimer’s disease, major depressive disorder, addiction, Parkinson’s disease, and peripheral and central nervous system injury diseases. Here, EGFR is linked to major depressive disorder.