TRPV5

TRPV5 is a calcium-selective ion channel of the transient receptor potential vanilloid (TRPV) family, primarily expressed in the kidney where it mediates apical Ca2+ entry into epithelial cells of the distal convoluted tubule and connecting tubule as part of transcellular calcium reabsorption. By allowing Ca2+ entry, TRPV5 contributes to systemic calcium homeostasis, working with basolateral transporters such as NCX1 and PMCA1 and with calbindin-D28k that shuttles Ca2+ to the basolateral side.

Structurally, TRPV5 forms a homotetramer. Each subunit has six transmembrane segments, with a pore loop between S5 and S6 that creates a selective Ca2+ permeation pathway. The channel is voltage-insensitive and highly selective for Ca2+. Its activity is modulated by intracellular Ca2+ via calmodulin, providing calcium-dependent inactivation, and by trafficking and hormonal signals that control its apical localization. Pharmacological blockers such as ruthenium red and gadolinium can inhibit TRPV5.

Expression and regulation: TRPV5 is enriched at the apical membrane of distal nephron cells. Calcitriol (1,25-dihydroxyvitamin D3) upregulates TRPV5 expression and promotes Ca2+ reabsorption, and parathyroid hormone also influences its function. Surface presence is controlled by trafficking, including endosomal recycling, adjusting Ca2+ entry according to physiological needs.

Clinical relevance: Altered TRPV5 function affects renal calcium handling and can contribute to disorders of calcium balance; in animal models, TRPV5 disruption causes hypercalciuria and bone changes. TRPV5 remains a focus of research on kidney calcium homeostasis and its regulation.