PANoptosis is a novel form of cell death that combines features of pyroptosis, apoptosis, and necroptosis. This process can be induced by various stimuli and involves the integration of multiple pro-cell death components, which assemble into different types of large molecular complexes known as PANoptosomes. Its regulatory mechanism involves several upstream key molecules, including Interferon Regulatory Factor 1, Transforming Growth Factor-β-Activated Kinase 1, and Adenosine Deaminase Acting on RNA 1, which collectively contribute to the initiation and execution of PANoptosis. Targeting the associated regulatory pathways represents an effective strategy for modulating PANoptosis. Given its significant role in cardiovascular diseases, modulating the activation of PANoptosis—either through promotion or inhibition—may offer a promising approach to preventing the progression of various related conditions. This review summarizes the current understanding of PANoptosis mechanisms and recent advances in research on its critical role in diabetic cardiomyopathy. It also highlights the complex crosstalk among multiple programmed cell death pathways, aiming to provide novel insights into effective therapeutic strategies for diabetic cardiomyopathy.
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