This paper presents the induced-proximity model for caspase activation, which explains how the first proteolytic signal is generated during apoptosis. Caspases are a family of cysteine-dependent, aspartic-specific proteases essential for apoptosis. The model suggests that the activation of caspases occurs through an unusual property of their zymogens, which can autoprocess to an active form. This autoprocessing is driven by intrinsic activity within the zymogens of initiator caspases. The model is supported by evidence showing that the death-inducing signaling complex (DISC) forms after the clustering of initiator caspase zymogens, leading to their activation. The DISC includes Fas, FADD, and caspase-8. The activation of caspase-8 is crucial for initiating apoptosis. The zymogen of caspase-8 can be processed by other zymogens, leading to the activation of the first protease in the cascade. The induced-proximity model proposes that the clustering of zymogens, facilitated by adapter molecules, brings them into close proximity, allowing for autoprocessing and activation. The model is further supported by experiments showing that the zymogen form of caspase-8 retains substrate specificity but processes substrates at a much lower rate than the fully processed enzyme. This zymogenicity is crucial for the regulation of caspase activity. The hypothesis is tested using an artificial death switch, where the zymogen form of caspase-8 is modified to be "frozen," allowing for the study of its activity. The model is consistent with the involvement of other caspases, such as caspase-9 and CED3, in similar proximity activation mechanisms. However, the model has limitations, particularly regarding the exact molecular mechanisms and the role of other proteins in the DISC. Future research aims to clarify these uncertainties, including the need for specific alignment of zymogens, the role of dimerization, and the minimal components of the DISC. Understanding these aspects is essential for developing therapeutic strategies to modulate apoptosis.This paper presents the induced-proximity model for caspase activation, which explains how the first proteolytic signal is generated during apoptosis. Caspases are a family of cysteine-dependent, aspartic-specific proteases essential for apoptosis. The model suggests that the activation of caspases occurs through an unusual property of their zymogens, which can autoprocess to an active form. This autoprocessing is driven by intrinsic activity within the zymogens of initiator caspases. The model is supported by evidence showing that the death-inducing signaling complex (DISC) forms after the clustering of initiator caspase zymogens, leading to their activation. The DISC includes Fas, FADD, and caspase-8. The activation of caspase-8 is crucial for initiating apoptosis. The zymogen of caspase-8 can be processed by other zymogens, leading to the activation of the first protease in the cascade. The induced-proximity model proposes that the clustering of zymogens, facilitated by adapter molecules, brings them into close proximity, allowing for autoprocessing and activation. The model is further supported by experiments showing that the zymogen form of caspase-8 retains substrate specificity but processes substrates at a much lower rate than the fully processed enzyme. This zymogenicity is crucial for the regulation of caspase activity. The hypothesis is tested using an artificial death switch, where the zymogen form of caspase-8 is modified to be "frozen," allowing for the study of its activity. The model is consistent with the involvement of other caspases, such as caspase-9 and CED3, in similar proximity activation mechanisms. However, the model has limitations, particularly regarding the exact molecular mechanisms and the role of other proteins in the DISC. Future research aims to clarify these uncertainties, including the need for specific alignment of zymogens, the role of dimerization, and the minimal components of the DISC. Understanding these aspects is essential for developing therapeutic strategies to modulate apoptosis.