The appendix provides detailed supplementary data and figures supporting the main findings of the study. It includes: 1. **Figure S1**: Demonstrates the essential role of GSDMD in caspase-1-mediated cell death and cytokine release, using osmoprotection assays and LPS-primed macrophages infected with *S. typhimurium*. 2. **Figure S2**: Shows the membrane targeting of endogenous GSDMD in LPS-primed macrophages, through immunoblot analysis and fractionation. 3. **Figure S3**: Characterizes the stability and monomeric state of purified full-length GSDMD, using gel filtration, SDS-PAGE, and thermofluor assays. 4. **Figure S4**: Investigates the cleavage and cell death activity of GSDMD104N, comparing it to wild-type GSDMD in terms of cleavage kinetics and LDH release. 5. **Figure S5**: Presents raw data from liposome dye release experiments, showing the fluorescence intensity over time and the effects of GSDMD and caspase-1. 6. **Figure S6**: Visualizes the formation of GSDMDNterm pores by cryo-EM, including micrographs at different time points and the average liposome diameter. 7. **Figure S7**: Controls experiments to show that full-length GSDMD adsorbed to mica does not form defined oligomeric structures, using atomic force microscopy (AFM). 8. **Figure S8**: Predicts the secondary structure of human GSDMD using Jpred, highlighting the caspase-1-cleavage site. These figures collectively support the mechanism of pyroptotic cell death through GSDMD membrane pore formation.The appendix provides detailed supplementary data and figures supporting the main findings of the study. It includes: 1. **Figure S1**: Demonstrates the essential role of GSDMD in caspase-1-mediated cell death and cytokine release, using osmoprotection assays and LPS-primed macrophages infected with *S. typhimurium*. 2. **Figure S2**: Shows the membrane targeting of endogenous GSDMD in LPS-primed macrophages, through immunoblot analysis and fractionation. 3. **Figure S3**: Characterizes the stability and monomeric state of purified full-length GSDMD, using gel filtration, SDS-PAGE, and thermofluor assays. 4. **Figure S4**: Investigates the cleavage and cell death activity of GSDMD104N, comparing it to wild-type GSDMD in terms of cleavage kinetics and LDH release. 5. **Figure S5**: Presents raw data from liposome dye release experiments, showing the fluorescence intensity over time and the effects of GSDMD and caspase-1. 6. **Figure S6**: Visualizes the formation of GSDMDNterm pores by cryo-EM, including micrographs at different time points and the average liposome diameter. 7. **Figure S7**: Controls experiments to show that full-length GSDMD adsorbed to mica does not form defined oligomeric structures, using atomic force microscopy (AFM). 8. **Figure S8**: Predicts the secondary structure of human GSDMD using Jpred, highlighting the caspase-1-cleavage site. These figures collectively support the mechanism of pyroptotic cell death through GSDMD membrane pore formation.