Slc26a9, a member of the SLC26A family of anion transporters, functions as a Cl-transporter and is involved in transepithelial Cl-and HCO3-transport, which is crucial for maintaining acid-base homeostasis in multiple organs [1,3]. It is expressed in the gastrointestinal tract, respiratory system, male tissues, and skin [1]. In the airway, it may secrete HCO3-to maintain proper airway surface liquid (ASL) pH, and in the alveolar space, it may support fluid reabsorption [1]. In the stomach, it acts as a Cl-uniporter in the gastric mucosa [4].

Slc26a9-knockout animals die early from neonatal distress, suggesting its importance in maintaining normal physiological function in the alveolar space [1]. In mice, both complete and parietal cell-selective Slc26a9 deletion causes the spontaneous development of gastric premalignant and malignant lesions, indicating its role in preventing gastric carcinogenesis [4]. In colorectal cancer cell lines, down-regulation of SLC26A9 induced cell cycle arrest, apoptosis, and inhibited cell proliferation and xenograft tumor growth, revealing its role in promoting colorectal tumorigenesis by modulating the Wnt/β-catenin signaling pathway [2].

In conclusion, Slc26a9 is essential for maintaining normal physiological functions such as fluid and ion transport in multiple organs. Gene-knockout mouse models have revealed its significance in diseases like gastric cancer and colorectal cancer, highlighting its potential as a therapeutic target in these disease areas.