Targeting ATP12A, a Nongastric Proton Pump α Subunit, for Idiopathic Pulmonary Fibrosis Treatment

Idiopathic pulmonary fibrosis (IPF) is characterized by lung injury and subsequent fibrotic response, leading to thickened alveolar walls and reduced alveolar space. The cause of IPF is unknown, and effective treatments are lacking. Similar to cystic fibrosis, IPF exhibits features of small airway disease and mucus accumulation. Researchers have found that the ATP12A gene, responsible for encoding the α-subunit of a certain protein involved in airway fluid acidification, may play a role in IPF pathogenesis. Overexpression of ATP12A was observed in IPF patients' distal small airways and exacerbated pulmonary fibrosis in mice. Blocking ATP12A with vonoprazan, a proton pump inhibitor, showed promise as a potential therapeutic approach for IPF.