TRPV5 is a highly calcium-selective cation channel that functions as the apical entry mechanism for transcellular calcium transport in the kidney distal convoluted tubule and intestine 1. As a constitutively active channel, TRPV5 mediates calcium influx as the first step in reabsorbing filtered calcium, with activity modulated by intracellular calcium levels through inward rectification and calcium-dependent inactivation 2. TRPV5 expression and activity respond dynamically to hormonal regulators including 1,25-dihydroxyvitamin D3, parathyroid hormone, estrogen, and testosterone, enabling fine-tuning of systemic calcium homeostasis 1. The channel's activity is further modulated by binding partners (calbindin-D28k, calmodulin, klotho), intracellular factors (magnesium, phosphate, protons), and fluid flow 1. Clinically, TRPV5 dysfunction associates with hypercalciuria and kidney stone disease; genetic variants identified in genome-wide association studies link TRPV5 polymorphisms to recurrent kidney stone formation, particularly in African populations where selective pressure has enriched specific alleles 31. TRPV5 mutations cause pathological calcium wasting, making it a therapeutic target for disorders with altered calcium metabolism and bone disease 1.