Even if the exact role of ErbB-mGluRI crosstalk in pathology will require dedicate investigations, in this context it is important to emphasize that, independently, either aberrant mGluRI functioning or altered NRGs/ErbB signaling have been repeatedly associated to various brain illnesses, including schizophrenia, bipolar disorder, autism spectrum disorders and genetic intellectual disabilities, as well as Alzheimer’s disease, major depressive disorder, Parkinson’s disease, and addiction [2,3,4,56,57,61,72,73,74,75,76,77,78,79,80,81,87,88,89,90,91,92,93,94,95,96,97,98,99,100]. Here, EGFR is linked to early-onset autosomal dominant Alzheimer disease.