Caspases in PANoptosis

Recent studies prove that the three well-established cell death pathways-pyroptosis, apoptosis, and necroptosis-are not isolated but rather engage in extensive crosstalk. PANoptosis, a newly identified pathway of inflammatory regulated cell death (RCD), integrates characteristics of apoptosis, pyroptosis, and necroptosis. Caspases are a family of conserved cysteine proteases that play critical roles in pyroptosis, apoptosis, and necroptosis. Similarly, caspases also play a role in PANoptosis. In this paper, we review the molecular mechanisms of these three RCDs and the crosstalk between them. We also delineate the discovery of PANoptosis and its association with disease. Furthermore, we discuss the caspase function in PANoptosis, mainly focusing on caspase-6 and caspase-8 molecules. This review describes the key molecules, especially caspases, in the context of PANoptosis research, aiming to provide a foundation for targeted interventions in PANoptosis-associated diseases.