The cellular membranes in humans, and in any other living cell, are composed of greasy molecules termed "lipids". While originally deemed as a simple medium, we now know that lipids are significant functional regulators for a variety of membrane proteins, including ligand-gated ion channels. As the name suggests, these channels are regulated by binding of specific chemical messengers, e.g., neurotransmitters in the brain, that induce opening of a pore for ions to travel from one side of the membrane to the other. A recent collaborative research between the Center and the group of Claudio Grosman focused on how lipids control the coupling between ligand binding and pore opening. Determining atomic-resolution structures of a ligand-gated ion channel complemented by simulations and free energy calculations performed with NAMD, we show that the response of the channel to ligand binding is completely eliminated in the absence of specific lipids required for activity. Our work highlights how specific protein-lipid interactions are involved in modulating protein functions, and paves the way for further examination of protein activities in complex membrane environments.