The human intestine Na⁺ Channel (hINaC) belongs to the DEG/ENaC gene family, it is the ortholog of the Brain Liver Intestine Na⁺ Channel (BLINaC) from mouse and rat. While BLINaC is expressed in various tissues, the expression of hINaC is restricted to the intestinal tract. We have recently shown that BLINaC from mouse (mBLINaC) is a constitutively active, Na⁺-selective channel when expressed in Xenopus oocytes, whereas BLINaC from rat (rBLINaC) is almost completely blocked by physiological concentrations of extracellular Ca²⁺. Consequently removal of extracellular Ca²⁺ activates the channel. In addition we found that rBLINaC can be inhibited by Diminazene (DIMI) and activated by flufenamic acid (FFA). Here we report the characterization of hINaC. Similar to rBLINaC, hINaC is also inactive when expressed in Xenopus oocytes. In addition, removal of extracellular Ca²⁺ leads to robust hINaC currents, which are mainly carried by Na⁺, suggesting that hINaC, like rBLINaC, is inactive under physiological concentrations of extracellular Ca²⁺. Furthermore we show that micromolar concentrations of DIMI block hINaC, whereas millimolar concentrations of FFA activate hINaC, supporting the hypothesis that hINaC requires an endogenous ligand in order to be activated. Taken together our results suggest a close functional relation between hINaC and rBLINaC, which will help to unravel the physiological function of hINaC.