Based on our findings, we propose a model in which increased excitatory neurotransmission in cortical neurons due to increased presynaptic Ca2+ influx via the interaction of N-type voltage Ca2+ channels with mutant HTT proteins can increase the activation of NMDARs, thereby inducing excitotoxicity in cortical and striatal neurons, ultimately leading to the progressive loss of these neurons in HD. This evidence concerns the gene HTT and Huntington disease.