Gasdermin D (GSDMD) is a two‑domain cytosolic protein that acts as the principal effector of pyroptosis. In its full‑length, uncleaved state, GSDMD adopts an autoinhibited conformation in which the C‑terminal domain (CT‑GSDMD) binds and suppresses the pore‑forming N‑terminal domain (NT‑GSDMD), thereby preventing premature membrane damage. Upon activation of canonical or non‑canonical inflammasomes, inflammatory caspases (primarily caspase‑1, ‑4, and ‑5 in humans) specifically cleave GSDMD at the aspartate residue 275 (Asp275) within the flexible interdomain linker. This proteolytic event separates the inhibitory CT‑domain from the NT‑domain, yielding the active cleaved GSDMD (Asp275) fragment-commonly referred to as NT‑GSDMD p30. The liberated N‑terminal fragment then translocates to the plasma membrane, oligomerizes, and inserts into the lipid bilayer to form large β‑barrel pores, which disrupt osmotic homeostasis, cause cell swelling and lysis, and facilitate the release of pro‑inflammatory cytokines such as IL‑1β and IL‑18. Thus, while full‑length GSDMD serves as a dormant guardian that maintains cellular integrity, cleaved GSDMD at Asp275 represents the irreversible executioner that triggers inflammatory cell death, underscoring Asp275 as the critical molecular switch that governs pyroptotic signaling.