The bestrophin (Best) protein family and its function as chloride channels have not been well characterized. Bestrophin-3 is suggested to induce Ca²⁺ activated currents in various tissues. We observed that rat Best-3 was upregulated by Cd²⁺ (25mM, 6h) both at the transcriptional and translational levels, in rat kidney PTC. Similar effects were observed with endoplasmic ER-stress inducing agents, such as thapsigargin (3mM, 6h) and tunicamycin (6mM, 6h) but not with the calcium ionophore A21387 (1mM, 3 and 6h). The upregulation of Best-3 by Cd²⁺ was partly dependent on ROS because it could be prevented by the antioxidant a- tocopherol (100mM). The regulation of Best-3 expression was also dependent on ERK1/2, which is known to be activated by Cd²⁺, because the ERK1/2 inhibitor U0126 (10mM) prevented Cd²⁺ -induced Best-3 upregulation. Current studies aim to identify the transcription factor/s involved in Best-3 gene expression. Our findings suggest that Best-3 plays a role in ER stress response induced by Cd²⁺ and other compounds and is regulated by ROS and ERK1/2 signaling. Funded by DFG TH 345/10-1.