<p>ANoptosis represents a unique form of programmed cell death that amalgamates the core characteristics of pyroptosis, apoptosis, and necroptosis, yet it constitutes a distinct pathway beyond the scope of any single one of them. During pathogen infection, PANoptosis is regulated by multi-protein complexes called PANoptosomes, which sense specific stimuli, including viral, bacterial, or fungal components, ultimately resulting in PANoptosis. This process contributes to pathogen clearance as well as excessive inflammatory response. Additionally, in some diseases such as renal damage, myocardial disease, nervous system diseases, and various cancers, PANoptosis influences disease occurrence, progression, and treatment outcomes. Targeting PANoptosis represents a promising way to enhance immune responses and achieve disease treatment in systemic disorder. This review synthesizes the current state of knowledge regarding the molecular mechanisms underlying PANoptosis in pathogen infection and systemic diseases, highlighting its role in pathological processes.</p> Graphical Abstract <p>Pathogens infection and multiple diseases are related with PANoptosis. The pathophysiologic mechanism of some diseases such as circulation system diseases, nervous system diseases, urinary system disease, the occurrence and progress of many tumor and multiple virous pathogens infection induced host immune response are related with PANoptosis.</p> <p></p>