The cleavage of GSDMD by human neutrophil lysate was inhibited by ELANE‑specific inhibitors in a dose‑dependent manner (Kambara H et al. 2018). The identified ELANE cleavage site C268 in human GSDMD is different from the caspase cleavage site D275 and is not conserved between humans and mice (Kambara H et al. 2018). The N‑terminal fragment of GSDMD (1‑268) formed oligomers and induced lytic cell death upon overexpression in human embryonic kidney HEK293 cells (Kambara H et al. 2018). High‑resolution total internal reflection fluorescence (TIRF) microscopy showed that after NET formation GSDMD localized to the plasma membrane in human primary neutrophils (Sollberger G et al. 2018). These data suggest that GSDMD cleavage by ELANE at D268 induces lytic cell death in neutrophils (Sollberger G et al. 2018; Kambara H et al. 2018). In addition, the N‑terminal fragment of GSDMD was shown to target azurophilic (primary) granules and autophagosomes in human and murine neutrophils (Karmakar M et al. 2020). In this study the N‑terminal fragment of GSDMD facilitated release of ELANE into the cytosol by permeabilization of azurophilic granules and secretion of IL‑1β via an autophagy machinery‑dependent pathway (Karmakar M et al. 2020).