The BCL-2 family of proteins plays a crucial role in apoptosis, a genetically programmed form of cell death. These proteins, which include both pro-apoptotic and anti-apoptotic members, reside primarily in mitochondria and other organelles. The BCL-2 family members possess conserved BCL-2 homology (BH) domains, particularly BH3, which is critical for their function. Pro-apoptotic members like BAX and BAK can form heterodimers with anti-apoptotic members like BCL-2 and BCL-XL, inhibiting their anti-apoptotic activity. Following a death signal, pro-apoptotic members undergo conformational changes, leading to their activation and translocation to the mitochondrial membrane, where they cause mitochondrial dysfunction, including changes in membrane potential, production of reactive oxygen species, and release of cytochrome c. Cytochrome c then activates caspases, leading to cell death. The BCL-2 family members also regulate mitochondrial function through channels or by modulating existing channels. Some pro-apoptotic members, such as BID, can function independently of anti-apoptotic members, suggesting they may act as sentinels for cellular damage. The BCL-2 family's role in apoptosis is complex and involves multiple mechanisms, including caspase-independent pathways and both mitochondria-dependent and mitochondria-independent pathways.The BCL-2 family of proteins plays a crucial role in apoptosis, a genetically programmed form of cell death. These proteins, which include both pro-apoptotic and anti-apoptotic members, reside primarily in mitochondria and other organelles. The BCL-2 family members possess conserved BCL-2 homology (BH) domains, particularly BH3, which is critical for their function. Pro-apoptotic members like BAX and BAK can form heterodimers with anti-apoptotic members like BCL-2 and BCL-XL, inhibiting their anti-apoptotic activity. Following a death signal, pro-apoptotic members undergo conformational changes, leading to their activation and translocation to the mitochondrial membrane, where they cause mitochondrial dysfunction, including changes in membrane potential, production of reactive oxygen species, and release of cytochrome c. Cytochrome c then activates caspases, leading to cell death. The BCL-2 family members also regulate mitochondrial function through channels or by modulating existing channels. Some pro-apoptotic members, such as BID, can function independently of anti-apoptotic members, suggesting they may act as sentinels for cellular damage. The BCL-2 family's role in apoptosis is complex and involves multiple mechanisms, including caspase-independent pathways and both mitochondria-dependent and mitochondria-independent pathways.