TRPV4

TRPV4 is a Ca²⁺-permeable, nonselective cation channel that confers sensitivity to extracellular osmolarity and functions as a vertebrate osmoreceptor^[1][2]. Mechanistically, TRPV4 converts osmotic and mechanical inputs into Ca²⁺ signaling, including cartilage loading responses that regulate extracellular matrix biosynthesis^[3]. In pulmonary fibrosis models, TRPV4 activity supports TGF-β1-dependent myofibroblast differentiation, and TRPV4-deficient mice show protection from fibrosis^[4]. Disease genetics further links TRPV4 mutations to Charcot-Marie-Tooth disease type 2C and skeletal dysplasia phenotypes^[5][6]. Compared with related TRPV isoforms, TRPV4 is distinguished by repeated experimental use in osmotic, mechanical-loading, endothelial, cartilage, and fibroblast mechanotransduction models^[1][3][4]. For experimental applications, GSK1016790A serves as a selective TRPV4 agonist, whereas GSK2193874 is an orally active TRPV4 blocker that prevented and resolved pulmonary edema in heart-failure models^[7][8].