GSDME and alopecia: Notably, several mutations in mouse GSDMA3 interfere with autoinhibition interfaces I and II, leading to the protein’s autoactivation and causing alopecia in mice.84,85 Additionally, several gain-of-function variants of GSDME (DFNA5) have been linked to autosomal dominant hearing loss in humans.28 This mutated, autoactive form of GSDME arises from exon 8 skipping, which results in a truncated GSDM-CT domain and subsequent loss of autoinhibition.