CARD8 is a caspase recruitment domain protein that forms a cytosolic inflammasome complex critical for innate immunity 1. Under resting conditions, CARD8's N-terminal domain auto-cleaves and binds the C-terminal fragment, maintaining inflammasome inactivity 2. Upon pathogen detection or cellular stress, proteasome-mediated degradation of the N-terminal fragment releases the C-terminal fragment, which polymerizes to assemble the CARD8 inflammasome 3. This active complex recruits and activates pro-caspase-1, leading to cleavage of gasdermin-D (GSDMD) and triggering pyroptotic cell death 4. CARD8 senses diverse danger signals, including HIV protease activity 2, ribotoxic stress 5, and DPP8/9 inhibitors 3. Importantly, CARD8-mediated pyroptosis of infected cells without productive infection provides an antiviral defense mechanism, though excessive activation contributes to pathogenesis 6. Disease-associated mutations in CARD8 link to auto-inflammatory and autoimmune disorders 1. CARD8 also negatively regulates NLRP3 inflammasome assembly and NF-κB signaling, suggesting broader immunomodulatory roles 7. This multifunctional inflammasome sensor represents a therapeutic target for controlling both infectious and inflammatory diseases.