Caspase substrates are vital proteins cleaved during apoptosis, playing key roles in cell death and other biological processes. This review summarizes over 280 known caspase substrates, highlighting their functions in apoptosis, cell cycle regulation, differentiation, and other cellular processes. Caspase cleavage can either inactivate or activate proteins, influencing cell morphology, signaling, and survival. For example, cleavage of ICAD releases CAD, a nuclease involved in DNA fragmentation, while cleavage of acinus contributes to chromatin condensation. Caspases also regulate cell adhesion, cytoskeletal dynamics, and nuclear structure. In signal transduction, caspases can inactivate antiapoptotic kinases like Akt and Raf-1, or activate proapoptotic pathways. Some caspase substrates, such as Bid, are cleaved to generate active fragments that promote apoptosis. Caspase cleavage can also lead to the release of cytokines like EMAP-II, which may aid in the engulfment of apoptotic cells. Caspase substrates are involved in various diseases, including neurodegenerative disorders like Huntington's disease and Alzheimer's disease, where caspase cleavage contributes to protein aggregation and neuronal death. Caspases also play a role in cell cycle regulation, with cleavage of proteins like Wee1 and p21 affecting cell cycle progression. In differentiation processes, caspases are involved in the maturation of cells such as macrophages and muscle cells. However, the exact mechanisms of caspase substrate cleavage and its regulation remain unclear, with factors like caspase specificity, subcellular localization, and the presence of antiapoptotic molecules influencing the outcome. Caspase cleavage can also contribute to the balance between apoptosis and necrosis, with PARP cleavage playing a key role in maintaining cellular energy during apoptosis. Overall, caspases are not only involved in cell death but also in a wide range of cellular processes, highlighting their complex and multifaceted roles in biology.Caspase substrates are vital proteins cleaved during apoptosis, playing key roles in cell death and other biological processes. This review summarizes over 280 known caspase substrates, highlighting their functions in apoptosis, cell cycle regulation, differentiation, and other cellular processes. Caspase cleavage can either inactivate or activate proteins, influencing cell morphology, signaling, and survival. For example, cleavage of ICAD releases CAD, a nuclease involved in DNA fragmentation, while cleavage of acinus contributes to chromatin condensation. Caspases also regulate cell adhesion, cytoskeletal dynamics, and nuclear structure. In signal transduction, caspases can inactivate antiapoptotic kinases like Akt and Raf-1, or activate proapoptotic pathways. Some caspase substrates, such as Bid, are cleaved to generate active fragments that promote apoptosis. Caspase cleavage can also lead to the release of cytokines like EMAP-II, which may aid in the engulfment of apoptotic cells. Caspase substrates are involved in various diseases, including neurodegenerative disorders like Huntington's disease and Alzheimer's disease, where caspase cleavage contributes to protein aggregation and neuronal death. Caspases also play a role in cell cycle regulation, with cleavage of proteins like Wee1 and p21 affecting cell cycle progression. In differentiation processes, caspases are involved in the maturation of cells such as macrophages and muscle cells. However, the exact mechanisms of caspase substrate cleavage and its regulation remain unclear, with factors like caspase specificity, subcellular localization, and the presence of antiapoptotic molecules influencing the outcome. Caspase cleavage can also contribute to the balance between apoptosis and necrosis, with PARP cleavage playing a key role in maintaining cellular energy during apoptosis. Overall, caspases are not only involved in cell death but also in a wide range of cellular processes, highlighting their complex and multifaceted roles in biology.