Caspases and programmed cell death in sepsis: mechanisms, pathophysiology, and therapeutic targets

Sepsis represents a critical medical condition characterized by organ impairment resulting from an uncontrolled systemic reaction to pathogenic infection, posing substantial difficulties in intensive care management. As a key pathological mechanism, programmed cell death (PCD) critically contributes to sepsis development, and caspases act as the central molecular hub governing multiple PCD modalities, including apoptosis, necroptosis, pyroptosis, and PANoptosis. In this manuscript, we review the classification and structural features of caspases, illustrate their molecular mechanisms in regulating the four PCD pathways, and clarify the dual pathological roles of these PCD forms in sepsis-induced immune dysregulation and organ damage. We also summarize therapeutic strategies targeting caspases and provide a theoretical basis for developing novel targeted treatments for sepsis.