The selective sodium hydrogen exchanger 3 (NHE3) inhibitor tenapanor is being developed by Ardelyx Inc. for the treatment of constipation-predominant irritable bowel syndrome (IBS-C) [under the tradename IBSRELA®] and for hyperphosphataemia in patients with chronic kidney disease (CKD) on dialysis or with end stage renal disease (ESRD). Based on positive results from the phase III T3MPO trial program, tenapanor was recently approved in the USA for the treatment of IBS-C in adults. This article summarises the milestones in the development of tenapanor leading to this first approval.