Versatility of gasdermin D beyond pyroptosis.

Gasdermin D (GSDMD) has garnered significant attention primarily for the pore-forming role of its p30 N-terminal fragment (NT-p30) generated during pyroptosis, a proinflammatory form of cell death. However, emerging evidence suggests that the formation of GSDMD-NT pores is reversible, and the activation of GSDMD does not necessarily lead to pyroptosis. Instead, this process may take part either in other forms of cell death, or in various state changes of living cells, including (i) inflammation regulation, (ii) endolysosomal pathway rewiring, (iii) granule exocytosis, (iv) type II immunity, (v) food tolerance maintenance, and (vi) temporary permeability alteration. This review explores the latest insights into the involvement of GSDMD in cell death and homeostasis maintenance, aiming to underscore the pleiotropic nature of GSDMD.