GSDMC

Gasdermin C (GSDMC) is a critical pore-forming protein belonging to the gasdermin superfamily, with its well-recognized alias being DFNA5L (Deafness Autosomal Dominant 5-Like), reflecting its sequence homology to the DFNA5 gene. It exerts its biological function primarily by mediating pyroptosis: upon activation, GSDMC undergoes conformational changes, oligomerizes on the cell membrane, and forms transmembrane pores. These pores disrupt cellular homeostasis, trigger cell lysis, and facilitate the release of pro-inflammatory cytokines such as IL-1β and IL-18.
GSDMC’s activation and expression are tightly modulated by signaling cascades including NF-κB and MAPK pathways, which are often triggered by pro-inflammatory stimuli like TNF-α. Dysregulated GSDMC is implicated in diverse pathologies, ranging from colorectal cancer—where it promotes tumor cell proliferation and metastasis—to inflammatory diseases such as psoriasis. In drug development, small-molecule compounds targeting GSDMC’s pore-forming activity are under preclinical investigation, though no candidates have advanced to clinical trials yet.