Gasdermin-B (GSDMB)

Gasdermin-B (GSDMB) is a member of the gasdermin family of pore-forming proteins involved in both cell death (pyroptosis) and non-lethal biological processes, such as epithelial differentiation and immune response[7][1][3][5]. GSDMB consists of an N-terminal domain responsible for membrane binding and pore formation, and a C-terminal domain that autoinhibits pore activity. Upon proteolytic cleavage (e.g., by granzyme A), the N-terminal domain is released, inserts into membranes, and forms lytic pores, causing cell death—a mechanism important in both host defense and cancer cell killing[3][5]. Multiple splicing isoforms (at least four with different linker regions) result in distinct functional outcomes; some isoforms cannot induce pyroptosis. GSDMB gene amplification or specific SNPs are linked with poor prognosis in HER2-positive cancers and increased risk of asthma and IBD, making it a potential disease biomarker and therapeutic target, although direct GSDMB-targeting drugs are not currently approved[1][3][6][7]. Its aberrant or context-dependent activity is a safety concern in therapeutic development.

Other names

Gasdermin BGSDMLPP4052PRO2521Gasdermin-like proteinGSDMB-1Gasdermin-B N-terminalGSDMB-NTp30Gasdermin-B C-terminalGSDMB-CTp16

Drugs or proteins (e.g., granzyme A) that cleave GSDMB at its interdomain linker release the N-terminal domain, enabling pore formation and induction of pyroptotic cell death[5]. Some pathogens (e.g., Shigella) produce effectors (IpaH7.8 ubiquitin ligase) that target and inactivate GSDMB or related gasdermins to suppress host cell pyroptosis[4][5].