Transient receptor potential cation channel subfamily V member 5 and Transient receptor potential cation channel subfamily C member 6 (TRPV5/TRPC6)

The TRPV5/TRPC6 and Ca2+ handling pathways comprise a network of ion channels and signaling molecules essential for maintaining systemic and cellular calcium balance, particularly in the renal system. Transient receptor potential cation channel subfamily V member 5 (TRPV5) acts as the primary gatekeeper for active calcium reabsorption in the kidney's distal convoluted tubule (UniProt: Q9HBA0). In contrast, Transient receptor potential cation channel subfamily C member 6 (TRPC6) is a non-selective cation channel found in glomerular podocytes, where it regulates structural integrity and signaling (UniProt: Q9Y210). Dysregulation of these pathways is heavily implicated in renal diseases; for instance, gain-of-function mutations in TRPC6 are a known cause of focal segmental glomerulosclerosis (FSGS), while TRPV5 deficiency leads to hypercalciuria and kidney stones (PubMed: 15864308). Pharmacological targeting of these pathways currently focuses on TRPC6 inhibitors, such as BI 764198 and GFB-887, to treat proteinuric kidney diseases by preventing podocyte damage (ClinicalTrials.gov: NCT04176536). Additionally, these channels are regulated by hormones like parathyroid hormone and Vitamin D, making them central to mineral metabolism disorders.

Other names

ECaC1CAT2FSGS2TRP6TRP5Transient receptor potential channel 6Transient receptor potential channel 5Calcium transport protein 2

Inhibition of TRPC6-mediated cation influx to protect podocyte integrity and modulation of TRPV5-mediated active calcium reabsorption in the distal nephron.