Slc26a9 is a member of the SLC26A family of anion transporters, functioning as a Cl-transporter across various epithelia [1,2,3,4,5,6,7,8,9,10]. It is involved in ion transport mechanisms and plays a role in maintaining acid-base homeostasis, especially in epithelia where it mediates Cl-absorption and HCO3-secretion [8]. It has been associated with pathways like Wnt/β-catenin signaling, and is of biological importance in multiple organs including the respiratory system, gastrointestinal tract, male tissues, and skin [1,3,6]. Genetic models such as gene-knockout (KO) mouse models have been crucial in studying its functions [1,6].

In Slc26a9-knockout animals, neonatal distress and early death occur, likely due to its role in fluid reabsorption in the alveolar space [1]. In the gastrointestinal tract, Slc26a9-deficient mice show spontaneous development of gastric premalignant and malignant lesions, with dysregulated differentiation of gastric stem cells, activated Wnt signaling, hyperproliferation, apoptosis inhibition, and metaplasia [6]. In colorectal cancer cell lines and mouse models, down-regulation of Slc26a9 induced cell cycle arrest and apoptosis, while inhibiting cell proliferation and xenograft tumor growth, indicating its role in promoting colorectal tumorigenesis through modulating Wnt/β-catenin signaling [3].

In conclusion, Slc26a9 is essential for maintaining proper ion and fluid balance in multiple organs. The study of Slc26a9 KO mouse models has revealed its role in various disease conditions, such as neonatal distress, gastric intraepithelial neoplasia, and colorectal cancer. Understanding its functions provides new possibilities for disease therapy, especially in diseases related to abnormal ion transport and epithelial cell homeostasis [1,3,6,8].