Just like the case made for PACAP in this very piece, it will be imperative to systematically evaluate all of the major players implicated in regulating energy homeostasis (including, but certainly not limited to, endocannabinoids, N/OFQ, NPY/AgRP neurons, POMC neurons, A10 dopamine neurons) not only under normophysiologic conditions but also under negative (e.g., fasting) and positive (e.g., obesity) energy balance states. Here, NPY is linked to obesity due to melanocortin 4 receptor deficiency.