The superfamily of cyclic nucleotide regulated cation channels includes the eukaryotic hyperpolarization-activated cyclic nucleotide-gated (HCN) and cyclic nucleotide gated (CNG) channels as well as a family of bacterial cyclic nucleotide regulated potassium channels. All of these channels are tetramers, with each subunit having 6 trans-membrane helices and a C-terminal cytosolic cyclic nucleotide binding (CNB) domain. The major difference between the eukaryotic and bacterial channels is the presence, in the eukaryotic membrane proteins, of a long linker (the C-linker) between the channel regions and the CNB domain. Despite this major difference, structural studies of the MlotiK1 bacterial channel (1,2,3) have provided general insights into the ligand-dependent conformational changes occurring in the CNB domains and about the structural properties of cation channels with 6 trans-membrane helices, such as voltage-gated potassium channels. This bacterial channel also displays specific properties that are very different from the properties of the eukaryotic channels (4). Interestingly, the recently determined structures of CNB-like domains from eukaryotic EAG channels have raised the possibility of novel molecular mechanisms of regulation by domains with this fold (5,6).