International Review of Cell and Molecular Biology
BH3-only proteins are proapoptotic members of the broader Bcl-2 family, which promote cell death by directly or indirectly activating Bax and Bak. The expression of BH3-only proteins is regulated both transcriptionally and posttranscriptionally in a cell type-specific and a tissue-specific manner. Research over the last 20 years has provided significant insights into their roles in tissue homeostasis and various pathologies, which in turn has led to the development of novel therapeutics for numerous diseases. In this review, a snapshot of the progress over this period is given, including our current understanding of their regulation, mode of action, role in mammalian development, and pathology.