Gasdermin-E (GSDME)

Gasdermin-E is a member of the gasdermin family encoded by the GSDME gene. It functions as a precursor protein that, upon cleavage by caspase 3 or granzyme B during apoptosis or immune attack, releases its N-terminal domain. This active fragment translocates to cellular membranes where it forms large pores (~10–15 nm), leading to an inflammatory form of programmed cell death called pyroptosis. While this mechanism can convert non-inflammatory apoptosis into immunogenic cell death—contributing to anti-tumor immunity and acting as a tumor suppressor—uncontrolled activation may also result in pathological inflammation and tissue injury. Mutations in GSDME are linked with hereditary hearing loss (DFNA5). The protein is expressed variably across tissues but is most abundant in placenta, kidney, muscle, brain cells, and cochlear hair cells; expression is often reduced in tumors. Targeting gasdermin-E holds promise for cancer therapy but poses challenges due to potential toxicity from excessive inflammatory responses.

Other names

DFNA5Gasdermin EGSDMEDeafness autosomal dominant 5 protein

Induction of pyroptosis via cleavage by caspase 3 or granzyme B, releasing the N-terminal fragment that forms membrane pores; Conversion of apoptosis to inflammatory pyroptotic cell death in response to chemotherapeutic drugs