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Therefore, many efforts have focused on neurodegenerative disease mechanisms and therapeutic strategies. Moreover, amyloid precursor proteins and their cleaving products, including APP-C31, may play important roles in neurodegeneration. This review provides a comprehensive introduction to the structure, neurotoxicity, regulatory mechanism, and relevance of APP-C31 to clinical diseases and its therapeutic potential as a drug target. This work will bridge the gap in our understanding of the function of APP-C31, which provides an experimental basis for neurodegenerative disease therapeutics. Meanwhile, a hypothesis is postulated that the APP-C31\u00a0functions not merely as a byproduct of caspase cleavage, but as the critical \"central executioner\" bridging upstream triggers and downstream neurodegeneration. Diverse upstream stressors, initiate the cascade to generate APP-C31. Once generated, C31 acts as a multi-functional signalling hub driving four distinct pathogenic pathways. 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