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Bcl-2-related proteins are critical regulators of cell survival that are localized to the outer mitochondrial, outer nuclear and endoplasmic reticulum membranes^1–4. Despite their physiological importance, the biochemical function of Bcl-2-related proteins has remained elusive. The three-dimensional structure of Bcl-x_L, an inhibitor of apoptosis, was recently shown to be similar to the structures of the pore-forming domains of bacterial toxins⁵. A key feature of these pore-forming domains is the ability to form ion channels in biological membranes^6,7. Here we demonstrate that Bcl-x_L shares this functional feature. Like the bacterial toxins, Bcl-x_L can insert into either synthetic lipid vesicles or planar lipid bilayers and form an ion-conducting channel. This channel is pH-sensitive and becomes cation-selective at physiological pH. The ion-conducting channel(s) formed by Bcl-x_L display multiple conductance states that have …