Despite the reviewed evidence, there remain many gaps in the field, including, but not limited to the following: (1) How Panx2, and potentially Panx3, fit into this puzzle, with more detailed research required on cardiac pannexin protein expression; (2) Pannexin’s role in the coronary vasculature; and (3) How pannexins contribute to cardiovascular disease with a metabolic basis. Here, PANX3 is linked to cardiovascular disorder.