AQP8 is a water channel protein that facilitates osmotic water transport across cellular membranes, including the plasma membrane, inner mitochondrial membrane, and endoplasmic reticulum 1. Beyond water, AQP8 transports uncharged molecules including hydrogen peroxide and ammonia (neutral form), but not urea or glycerol [UniProt sources cited in abstracts]. In hepatocytes, AQP8 localizes to the canalicular membrane where it mediates cAMP-induced water secretion critical for bile formation and dilution 2. AQP8 also facilitates hepatocyte mitochondrial ammonia uptake for urea metabolism and regulates hydrogen peroxide-dependent cholesterol synthesis [UniProt sources]. In the digestive system, AQP8 participates in pancreatic juice secretion 3 and intestinal water transport 4. Notably, AQP8 appears downregulated in colorectal carcinoma tissues compared to normal tissue 5, contrasting with its pro-proliferative role in glioma where overexpression enhances cell proliferation through Wnt/β-catenin pathway activation 6. The channel's water transport function is sensitive to mercury and copper inhibition [UniProt sources]. Recent evidence validates hepatocyte AQP8 as a therapeutic target; upregulation by the small molecule scutellarin increases bile flow and prevents gallstone formation in mice 2, suggesting AQP8 modulation may provide therapeutic benefit in biliary disorders.