Caspase-3 is a crucial protease in the process of apoptosis, playing a significant role in the execution of programmed cell death. Recent studies have revealed that caspase-3 is essential for certain apoptotic processes, such as chromatin condensation and DNA fragmentation, in a tissue-, cell type-, and death stimulus-specific manner. Caspase-3 is required for the activation of other caspases and the cleavage of specific substrates like α-fodrin, gelsolin, and ICAD/DFF-45, which are involved in the morphological changes associated with apoptosis. However, the activation of caspase-3 does not always depend on mitochondrial cytochrome c release or caspase-9 function. The absence of caspase-3 in knockout mice and cell lines has shown that it is indispensable for certain apoptotic events, but not all, suggesting that other caspases or proteases may compensate in specific contexts. The significance of cell death without morphological changes and DNA fragmentation remains a topic of interest, as it challenges the traditional view of apoptosis as a well-defined process. Overall, caspase-3's role in apoptosis is multifaceted, and further research is needed to fully understand its precise functions and mechanisms.Caspase-3 is a crucial protease in the process of apoptosis, playing a significant role in the execution of programmed cell death. Recent studies have revealed that caspase-3 is essential for certain apoptotic processes, such as chromatin condensation and DNA fragmentation, in a tissue-, cell type-, and death stimulus-specific manner. Caspase-3 is required for the activation of other caspases and the cleavage of specific substrates like α-fodrin, gelsolin, and ICAD/DFF-45, which are involved in the morphological changes associated with apoptosis. However, the activation of caspase-3 does not always depend on mitochondrial cytochrome c release or caspase-9 function. The absence of caspase-3 in knockout mice and cell lines has shown that it is indispensable for certain apoptotic events, but not all, suggesting that other caspases or proteases may compensate in specific contexts. The significance of cell death without morphological changes and DNA fragmentation remains a topic of interest, as it challenges the traditional view of apoptosis as a well-defined process. Overall, caspase-3's role in apoptosis is multifaceted, and further research is needed to fully understand its precise functions and mechanisms.