Aqp3, short for aquaporin 3 (Gill blood group), is an aquaglyceroporin belonging to the AQP family. It transports water, glycerol, small solutes, and hydrogen peroxide across the plasma membrane. Aqp3 is involved in various regulatory pathways, such as the PDPK1-AKT-MTOR axis, AMPK/SIRT1, and PPAR-γ/NF-κB axes, and is crucial for numerous biological processes including cell proliferation, migration, invasion, and redox regulation [1,2,3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In hepatocellular carcinoma cells, FBXW5-mediated degradation of Aqp3 suppresses autophagic cell death through the PDPK1-AKT-MTOR axis, indicating Aqp3's role in tumor cell behavior regulation [1]. In a mouse model of cholelithiasis, Aqp3 was significantly down-regulated. Overexpression of Aqp3 activated the AMPK/SIRT1 signaling pathway, reducing inflammatory injury of gallbladder mucosal epithelial cells and curbing gallstone formation [2]. In lung adenocarcinoma, Aqp3 promoted M2 macrophage polarization via the PPAR-γ/NF-κB axis, affecting tumor growth and migration. Aqp3 knockout mice models further revealed its role in mediating M2 macrophage polarization and modulating tumor glucose metabolism [3].

In conclusion, Aqp3 is essential for multiple biological functions, especially in processes related to cell behavior and redox regulation. Model-based research, particularly KO/CKO mouse models, has provided insights into its role in diseases such as hepatocellular carcinoma, cholelithiasis, and lung adenocarcinoma, offering potential therapeutic targets for these conditions.