A unique feature of the esophageal wall structure is its innermost mucosal layer, which has a stratified squamous epithelium with varying thicknesses and degrees of keratinization. For instance, in the rodent’s esophagus, squamous epithelial cells are organized in four to five layers and are usually keratinized. Meanwhile, in the thicker esophageal mucosa of humans and pigs, the squamous cells are arranged in up to 10–15 layers, and the epithelial surface is not keratinized. Sentient responses to chemical, thermal, and mechanical stimuli occur in the esophagus and epithelial ion transporters mediate many of these responses.

The transient receptor potential vanilloid 4 (TRPV4) channel is a non-selective cation channel that is widely expressed in different human tissues, including the alimentary canal, where it acts as a molecular sensor for different sensory modalities such as osmotic, mechanical, and thermal stimuli, and transduces these stimuli into signals that regulate a variety of functional activities. Despite the extensive research to determine the role of this channel in the physiology and pathophysiology of different organs, the unique morphological and functional features of the TRPV4 channel in the esophagus remain largely unknown.

A decade ago, the TRPV4 channel was shown to be highly expressed in the esophageal epithelial cells where its activation induces Ca²⁺-dependent exocytotic release of vesicular ATP, which, in turn, mediates several functions, ranging from mechanotransduction, mediated by the action of the released ATP on purinergic receptors expressed by vagal afferents, to wound healing, thought to be mediated indirectly by one the ATP metabolites, adenosine, produced by the action of the enzyme ectonucleotidases. This work summarizes the research progress on the TRPV4 channel and focuses on the functional expression of the TRPV4 channel in the esophageal epithelium and its possible role in different esophageal diseases that would support TRPV4 as a candidate target for future therapeutic approaches to treat patients with such conditions.