KCNH channels, which include the EAG, ERG and ELK channel subfamilies, are voltage-gated K+ channels involved in regulating electrical excitability in heart and nerve cells. Although related to the cyclic nucleotide–regulated HCN and CNG channels, they are not regulated by nucleotide binding. KCNH channels have an intracellular C-terminal cyclic nucleotide–binding homology domain (CNBHD) that is connected to the channel pore by a C-linker, and these regions are important for channel trafficking and function. However, there is no structural information on these C-terminal domains, so it is unclear what role they play in channel regulation. Now, Zagotta and colleagues have determined the structure of the C-linker/CNBHD from zebrafish ELK. Similarly to HCN channels, the C-linker is important for mediating intersubunit contacts, but the ELK C-linker/CNBHD forms dimers in the crystal and in solution, whereas the HCN C-linker/cyclic nucleotide binding domain (CNBD) is tetrameric. The ligand binding pocket of ELK CNBHD has a negatively charged electrostatic profile, making it an unfavorable site for binding by the negatively charged nucleotides, which may help explain its nucleotide independence. In addition, a tyrosine phenyl ring on the short C-terminal β9-strand of CNBHD sits at an equivalent position to the cAMP purine ring position in HCN CNBD. The authors find that mutating the tyrosine or deleting β9 causes a shift in ELK's voltage-dependent activation. So rather than being regulated by cyclic nucleotide–binding, the authors suggest that β9 may act as an intrinsic regulatory element. (Nature doi:10.1038/nature10735, published online 9 January 2012)