The Bcl-2 family of proteins is characterized by its ability to modulate cell death (apoptosis) under a broad range of physiologic conditions. Bcl-2 and several related proteins function to inhibit apoptosis, while other members of the Bcl-2 family, such as Bax, accelerate death under various conditions. One member of the Bcl-2 family, designated Bak, functions primarily to enhance apoptotic cell death following appropriate activating signals and counteracts the protection from apoptosis provided by Bcl-2. Expression of Bak is widespread in a broad range of cells, including various long-lived, terminally differentiated cell types, suggesting that its cell-death-inducing activity is broadly distributed and that the regulation of inhibitors of apoptosis may represent an important determinant of tissue-specific modulation of apoptosis.