AQP5 is a water channel protein that functions as a homotetrameric transmembrane channel, with each monomer independently mediating water transport across the plasma membrane along its osmotic gradient 1. In normal physiology, AQP5 plays a critical role in fluid secretion in salivary glands and is required for TRPV4 activation by hypotonicity, controlling regulatory volume decrease in salivary epithelial cells 2. AQP5 expression is downregulated in Sjögren's syndrome salivary glands during interferon-γ-induced ferroptosis, and restoration of AQP5 expression correlates with improved salivary gland function 34. Beyond fluid transport, AQP5 has emerged as a functional cancer stem cell (CSC) marker in gastric cancer, enriching for self-renewing populations capable of initiating and sustaining tumor progression. AQP5+ CSCs promote tumor growth and invasion through WNT, PI3K, and MAPK-dependent mechanisms, and coordinate with LGR5 to enhance malignant biological functions by activating autophagy and inducing ULK1 ubiquitination 56. AQP5 is also ectopically overexpressed in breast cancer, where it associates with lymph node metastasis, poor prognosis, and dysregulated epithelial cell-cell adhesion 7. In early gastric cardia adenocarcinoma, NNMT-mediated metabolism enriches AQP5+ stem cell populations that drive malignant progression 8. These findings position AQP5 as a potential prognostic biomarker and therapeutic target in cancer.