Apoptosis plays a major role in normal organism development, tissue homeostasis, and removal of damaged cells. Hrk, a pro-apoptotic member of the Bcl-2 homology domain-3 (BH3)-only group of the Bcl-2 family of proteins, was also identified as novel protein induced during programmed neuronal death. It lacks significant homology to other Bcl-2 family members except for an 8-amino acid region that is similar to the BH3 motif of Bik. Hrk regulates apoptosis through interaction with the anti-apoptotic proteins Bcl-2 and Bcl-XL via this domain. It does not interact with the pro-apoptotic proteins Bax, Bak, or Bcl-XS. Hrk localizes to mitochondrial membranes in a pattern similar to that previously reported for Bcl-2 and Bcl-XL.