Members in the Bcl-2 family are critical regulators of apoptosis by either inhibiting or promoting cell death. Bcl-2 homology 3 (BH3) domain is a potent death domain. BH3 domain containing pro-apoptotic proteins, including Bad, Bax, Bid, Bik, and Hrk, form a growing subclass of the Bcl-2 family. A novel BH3 domain containing protein was recently identified and designated Bcl-G. The mRNA of Bcl-G encodes 2 isoforms, Bcl-GL, which is widely expressed in multiple tissues, and Bcl-GS, which is only found in testis. The Bcl-GS protein is predominantly localized to cytoplasmic organelles whereas Bcl-GL was distributed throughout the cytosol. Overexpression of either protein induced apoptosis, although Bcl-GS was far more potent than Bcl-GS. Apoptosis induction was dependent on the BH3 domain and could be suppressed by co-expression with the anti-apoptotic Bcl-XL protein.