Transient receptor potential cation channel subfamily V member 4 (TRPV4) (TRPV4)

Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel that serves as a versatile polymodal sensor, responding to osmotic, mechanical, and thermal stimuli (UniProt Q9HBA0). It is widely expressed across various tissues, including the lungs, kidneys, skin, and musculoskeletal system, where it plays a pivotal role in maintaining calcium homeostasis and regulating cellular signaling pathways (PubMed: 30104301). In the vascular endothelium, TRPV4 is essential for maintaining barrier integrity and modulating vascular tone through the release of nitric oxide and hyperpolarizing factors (PubMed: 29453292). Genetic mutations in the TRPV4 gene are associated with a diverse group of disorders known as TRPV4-pathies, which include various skeletal dysplasias and hereditary motor and sensory neuropathies (NIH: MedlinePlus). From a therapeutic perspective, TRPV4 is an active target for drug development, particularly for treating pulmonary edema, heart failure, and chronic cough, with several small-molecule antagonists like GSK2798745 undergoing clinical evaluation (ClinicalTrials.gov). While targeting TRPV4 holds significant promise for managing fluid balance and inflammatory conditions, potential safety concerns such as impaired thermoregulation and effects on bone metabolism require careful monitoring during clinical development (PubMed: 28838911).

Other names

VRL-2TRP12OTRPC4VR-OACVanilloid receptor-like protein 2Osmoreceptor-sensitive calcium channel

TRPV4 modulators primarily function as antagonists to inhibit the influx of calcium and other cations, thereby reducing vascular permeability, inflammation, and pain signaling (PubMed: 28838911). Agonists are also used in research to activate the channel and study its role in mechanotransduction and osmotic regulation (PubMed: 10952311).