An elusive adenylate cyclase complicit in cholera is exposed.

The intestinal consequences of cholera enterotoxin are caused by activation of the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel through the actions of an as-yet-unknown adenylate cyclase. A new study hunts down this elusive enzyme, showing that mouse and human intestinal epithelium functionally and structurally pair adenylate cyclase isoform 6 (AC6) with CFTR. These findings provide important insights into the molecular mechanisms underlying the robust pathological activation of CFTR activity and promise new opportunities to treat cholera.