The human body carefully regulates the internal pH of different organs to maintain homeostasis. For example, while the blood plasma maintains a neutral pH of 7, the stomach lumen has an acidic pH of 1.5 - 3.5. The low pH of stomach lumen helps kill pathogens in the food and break down complex food molecules.

The acid-secreting gastric mucosal epithelial cells (parietal cells) lining the stomach lumen maintain the low pH in the lumen. Numerous ion transporters and channels on these parietal cells help regulate gastric acid secretion by precise ion transport and thus play an essential role in maintaining acid/base homeostasis. Of importance is the hydrogen-potassium ATPase, or the proton pump, a P-type ATPase, present on the parietal cells. Also known as the H⁺/K⁺ ATPase, these pumps acidify the stomach contents by exchanging potassium ions from the stomach lumen with hydrogen ions from the parietal cell cytoplasm. The hydrogen ions secreted by these hydrogen-potassium ATPases and the chloride ions secreted by the chloride channels on the parietal cells combine to form hydrochloric acid in the stomach lumen.

Due to medicines or infections, excessive acid secretion causes acid reflux, generally refered to as heartburn. In such cases, therapeutic drugs such as proton pump inhibitors help block the hydrogen-potassium ATPases, thereby reducing the release of hydrogen ions into the stomach lumen.