One of the most promising and novel strategies to interfere with neurological disease processes is gene therapy using recombinant adeno-associated viral (rAAV) vectors. Such a rAAV-based gene delivery approach is rapidly advancing towards clinical trials. In this regard, neuropeptide Y (NPY) gene transduction into the brain tissue has attracted particular interest due to its potential to regulate and perhaps even ameliorate epileptic conditions. NPY gene transduction by viral vectors in epileptogenic regions of the brain can effectively suppress seizures in animals. The mechanisms underlying the seizure-suppressant effects of an NPY transgene are not well understood; in particular, under which circumstances transgene NPY is released, and whether and how it acts on synaptic transmission within the area of viral vector transduction are not known. These questions are of fundamental importance not only for the implementation of such a gene therapy approach in clinical trials with patients, but also for our general understanding of how transgene neuropeptides may act in the brain.