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

Transient receptor potential cation channel subfamily V member 5 (TRPV5) is a highly calcium-selective ion channel of the TRP family, mainly expressed in the distal convoluted tubule of the kidney, where it mediates active calcium reabsorption critical for systemic calcium homeostasis[1][2][8]. The channel is characterized by six transmembrane domains, strong calcium selectivity, and inward rectification. TRPV5 forms homo- or heterotetramers (with TRPV6). It is regulated by a variety of endogenous factors, including calmodulin (CaM, which mediates calcium-dependent inactivation), phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2, which activates the channel), long-chain coenzyme A species (LC-CoA, activating), and α-klotho (which stabilizes the channel for greater reabsorption)[1][6][8]. Genetic deletion or inactivating mutations in TRPV5 disrupt renal calcium retention, causing urinary calcium wasting, secondary hyperparathyroidism, and bone loss. Recently, TRPV5 has also been implicated in B-cell function and immune response regulation[10]. Selective inhibitors include econazole and the research compound ZINC17988990, and structure-function studies are guiding drug discovery efforts for conditions related to abnormal calcium handling[8].

Other names

Calcium transport protein 1ECaC2TrpV5

Direct inhibition of channel activity (by small molecules like econazole and ZINC17988990)[1][8] Allosteric/channel pore blockade (/by inhibitors binding within the ion channels)[8] Modulation by endogenous ligands (e.g., activation by PI(4,5)P2, LC-CoA; inhibition by CaM)[6][8]