Transient receptor potential cation channel subfamily V member 5 (TRPV5) (TRPV5)

Transient receptor potential cation channel subfamily V member 5 (TRPV5) is a highly selective calcium-permeable ion channel that serves as the gatekeeper for active transcellular calcium reabsorption in the kidney [1, 2]. Located primarily in the apical membrane of the distal convoluted tubule (DCT) and connecting tubule (CNT), TRPV5 facilitates the entry of calcium from the pro-urine into the tubular cell, which is the rate-limiting step in renal calcium handling [2, 3]. Related channels, such as TRPV6, play a similar role primarily in the intestine, though they are also present in the kidney to a lesser extent [3]. Dysregulation of TRPV5 is associated with clinical conditions like idiopathic hypercalciuria, nephrolithiasis (kidney stones), and abnormalities in bone mineral density due to the tight coupling of renal calcium conservation and skeletal health [2, 4]. While direct pharmacological inhibitors or activators of TRPV5 are largely in the experimental stage, existing therapies like thiazide diuretics and vitamin D analogs exert their effects partly by modulating TRPV5 expression and activity [3, 5]. Understanding the regulation of this channel by hormones such as parathyroid hormone (PTH) and klotho is essential for developing targeted treatments for mineral metabolism disorders [1, 5].

Other names

ECaC1Calcium transport protein 1CAT1Transient receptor potential cation channel subfamily V member 5

TRPV5 functions as a calcium-selective pore that allows passive entry of Ca2+ ions from the tubular lumen into renal epithelial cells, driven by an electrochemical gradient. Drugs targeting this system either directly block the channel pore or modulate its surface expression and open probability through hormonal or signaling pathways to regulate systemic calcium levels.