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Cadmium (Cd) is an environmentally prevalent toxicant posing increasing risk to human health worldwide. Recent publications had identified cadmium ion (Cd 2+) as the substrate of the human organic cation transporter 2 (hOCT2), which might serve as one of the mechanism for cadmium accumulation in kidney. In contrast, little was known about how Cd 2+ could affect the function of hOCT2. Herein, we further investigated the effect of cadmium exposure on the activity of hOCT2. Interestingly, preliminary data from our lab showed that acute exposure (20 minutes) of Cd 2+ could significantly upregulate the activities of human hOCT2 in a dose-dependent manner, with little effect on the control cells (Figure 1). The upregulation was accompanied with a significant increase of the maximal transport rate (Vmax), while with a negligible change in the kinetic affinity constant (Km) of the probe substrate metformin (Figure 2 …