Calcium stone formation is mostly caused by urinary Ca2+ supersaturation. In order to prevent this, Ca2+ is reabsorbed throughout the kidney. In this organ, the proximal tubule (PT) is a major site of Ca2+ reabsorption, whereas the loop of Henle (LOH) downstream is the site where calcium phosphate crystals form as precursors to calcium stones. The majority of Ca2+ transport during reabsorption in the PT is mediated through paracellular transport, but it is unclear how much PT epithelia rely on transcellular movement of Ca2+. In their Research Article, Bidhan Bandyopadhyay and co-workers (Ibeh et al, 2019) now show that the Ca2+-sensing receptor (CSR) – the main mediator of transcellular transport in other parts of the nephron – activates transient receptor potential canonical 3 (TRPC3) channels in renal PT cells. In addition, CSR and TRPC3 colocalize and functionally interact at the apical luminal membrane in these cells. Importantly, the authors show that mice lacking TRPC3 display disrupted PT Ca2+ transport and presence of calcium phosphate crystals in the LOH. Taken together, this work demonstrates that PT cells employ a transcellular Ca2+ entry pathway as an important mechanism to prevent the build-up of calcium phosphate crystals as a first step in the formation of calcium stones.