Slc26a6, also known as putative anion transporter 1 (PAT1) and chloride/formate exchanger, is a member of the SLC26 family of multifunctional anion transporters. It is a versatile anion exchanger, capable of transporting various anions such as OXa2⁻, HCO3⁻, Cl⁻, and SO42⁻, and is involved in processes like fluid absorption, anion secretion, regulation of intracellular pH, and waste product elimination [1,2,6]. It plays a significant role in ion homeostasis and acid-base balance across multiple organs including the pancreas, kidney, intestine, and heart [1,6]. Genetic models, like knockout mice, have been crucial for studying its functions [3,4,5,7].

In Slc26a6 null mice, several phenotypes are observed. They exhibit hyperoxaluria and calcium oxalate urolithiasis due to defective intestinal back-secretion of ingested oxalate, suggesting SLC26A6's key role in oxalate homeostasis [4]. In the pancreas, deletion of Slc26a6 reduces stimulated juice secretion and HCO3⁻-dependent fluid secretion by about 35% [7]. In the intestine, loss of SLC26A6 function in PKO mice disrupts gut microbiome and related metabolites, decreases gut-barrier integrity, and increases susceptibility to intestinal inflammation [3].

In conclusion, Slc26a6 is essential for maintaining normal physiological functions related to anion transport and homeostasis. Studies using Slc26a6 KO mouse models have revealed its significance in diseases such as nephrolithiasis, inflammatory bowel diseases, and potentially in pancreatic disorders. Understanding its function provides insights into the pathophysiology of these diseases, potentially guiding the development of new therapeutic strategies [1,2,3,4,7].

References:

1. Wang, Juan, Wang, Wenkang, Wang, Hui, Tuo, Biguang. 2021. Physiological and Pathological Functions of SLC26A6. In Frontiers in medicine, 7, 618256. doi:10.3389/fmed.2020.618256. https://pubmed.ncbi.nlm.nih.gov/33553213/

2. Yang, Xingyue, Yao, Shun, An, Jiaxing, Wang, Hui, Tuo, Biguang. 2021. SLC26A6 and NADC‑1: Future direction of nephrolithiasis and calculus‑related hypertension research (Review). In Molecular medicine reports, 24, . doi:10.3892/mmr.2021.12385. https://pubmed.ncbi.nlm.nih.gov/34458928/

3. Anbazhagan, Arivarasu N, Ge, Yong, Priyamvada, Shubha, Mohamadzadeh, Mansour, Dudeja, Pradeep K. 2024. A Direct Link Implicating Loss of SLC26A6 to Gut Microbial Dysbiosis, Compromised Barrier Integrity, and Inflammation. In Gastroenterology, 167, 704-717.e3. doi:10.1053/j.gastro.2024.05.002. https://pubmed.ncbi.nlm.nih.gov/38735402/

4. Aronson, Peter S. . Role of SLC26A6-mediated Cl⁻-oxalate exchange in renal physiology and pathophysiology. In Journal of nephrology, 23 Suppl 16, S158-64. doi:. https://pubmed.ncbi.nlm.nih.gov/21170874/

5. Song, Ying, Ishiguro, Hiroshi, Yamamoto, Akiko, Jin, Chun Xiang, Kondo, Takaharu. . Effects of Slc26a6 deletion and CFTR inhibition on HCO3- secretion by mouse pancreatic duct. In The journal of medical investigation : JMI, 56 Suppl, 332-5. doi:. https://pubmed.ncbi.nlm.nih.gov/20224218/

6. Seidler, Ursula E. 2025. The enigmatic SLC26A6 multifunctional anion transporter: recent advances in structure-function relationship, pathophysiological significance and novel pharmacological inhibitors. In Frontiers in pharmacology, 15, 1536864. doi:10.3389/fphar.2024.1536864. https://pubmed.ncbi.nlm.nih.gov/39949394/

7. Munemasa, Takashi, Mukaibo, Taro, Melvin, James E. 2019. Slc26a6 is an apical membrane anion exchanger that drives HCO3--dependent fluid secretion in murine pancreatic acinar cells. In American journal of physiology. Cell physiology, 317, C1153-C1160. doi:10.1152/ajpcell.00257.2019. https://pubmed.ncbi.nlm.nih.gov/31532720/