Evaluation of: Tsai MF, Li M, Hwang TC. Stable ATP binding mediated by a partial NBD dimer of the CFTR chloride channel. J. Gen. Physiol. 135(5), 399-414 (2010). The cystic fibrosis transmembrane conductance regulator (CFTR) is an ATP binding cassette transporter forming a chloride (Cl(-)) channel whose opening/closing (a mechanism named gating) depends on a complex regulation by the phosphorylation/dephosphorylation of the regulatory R-domain and ATP binding/hydrolysis occurring on nucleotide-binding domains. Understanding how the channel is gated by ATP is important, since many mutations in the CFTR gene causing cystic fibrosis are located in these nucleotide-binding domains, and the exact molecular mechanism linking the ATPase cycle to Cl(-) permeation remains unclear and controversial. In their recent paper, Tsai et al. examined the ATP gating of CFTR in great detail, highlighting new, exciting and provocative concepts.