Nephrolithiasis is a complex disease resulted from abnormal crystal deposition in renal tissues. The crystal-cell interaction represents a critical step in kidney stone formation, involving numerous genes and proteins. We previously identified endoplasmic reticulum (ER) stress as a key biological process in the crystal-cell interactions, the precise mechanism of which has remained unclear. In the present study, we found that calcium oxalate monohydrate (COM) crystals induced an overload of intracellular Ca