Box I Table I.

Characteristics of GSDM family members

GSDM	Mouse Ortholog	Lipid Binding	Proteolytic Activator	Biological Pathways	Physiological tissue expression	Associated diseases	Ref.
GSDMA (GSDM1, FKSG9)	Gsdma1 Gsdma2 Gsdma3	cardiolipin, phosphatidic acid, phospatidylserine, phosphoinositides	SpeBj Unknown human activator?	pyroptosis, mitochondrial homeostasis	esophagus, stomach, skin, mammary gland	systemic sclerosis, alopecia (only in mice), gastric cancer	[9,28,44–49]
GSDMB (GSDMLa)	None	for both NTh and FLi: phosphatidic acid, phosphatidyl glycerolsulfatide, phosphoinositides	GzmAk Caspases?	pyroptosis, adjuvant in GSDMD-mediated pyroptosis (FL), cell proliferation, migration, adhesion (FL), Gram− bacterial lysis	airways, gastrointestinal tract, liver, neuroendocrine cells, immune cells	asthma, IBD, type 1 diabetes, systemic sclerosis, colorectal, liver, pancreatic, breast, cervical, lung cancers	[9,13,16–19,28,29,31,33,47]
GSDMC (MLZEb)	Gsdmc1 Gsdmc2 Gsdmc3 Gsdmc4	uncharacterized	Caspase 8	pyroptosis	skin, gastrointestinal tract, trachea, spleen, bladder	colorectal cancer, melanoma	[9,28,47,50,51]
GSDMD (GSDMDC1c, DFNA5Ld, FKSG10)	Gsdmd	cardiolipin, phosphatidic acid, phosphoinositides	Caspases 1, 4, 5, 8 ELANEl Cathepsin G	pyroptosis, NETosisn, mitophagy, sublytic release of inflammatory mediators	immune cells, gastrointestinal tract, placenta	infection, sepsis, IBD, autoimmune encephalomyelitis, liver fibrosis, gastrointestinal, pancreatic, salivary gland cancers, melanoma, lymphoma	[9,28,35,47,52–61]
GSDME (DFNA5e, ICERE-1)	Dfna5, Gsdme	cardiolipin, phosphatidylserine, phosphoinositides	Caspase 3 GzmBm	pyroptosis, sublytic release of inflammatory mediators	cochlea, heart, brain, small intestine, colon, kidney, placenta	autosomal dominant hearing loss, acute kidney injury, IBD, gastric, colorectal, breast cancers, melanoma	[9,28,47,55,62–67]
PJVKf (DFNB59g, GSDMF?)	Pjvk, Dfbn59	uncharacterized	Unknown, not required?	pexophagy	brain, eye, inner ear, heart, lung, kidney, liver, testis	autosomal recessive auditory neuropathy, recessive non-syndromic hearing impairment	[9,28,47,68]

^aGSDML, gasdermin-like protein;

^bMLZE, melanoma-derived leucine zipper-containing extranuclear factor;

^cGSDMDC1, gasdermin domain-containing protein 1;

^dDFNA5L, DFNA5-like;

^eDFNA5, deafness, autosomal dominant 5;

^fPJVK, pejvakin;

^gDFNB49, deafness, autosomal recessive 59;

^hFL, full-length;

ⁱNT, N-terminal;

^jSpeB, streptococcal pyrogenic exotoxin B;

^kGzmA, granzyme A;

^lELANE, elastase neutrophil expressed;

^mGzmB, granzyme B;

ⁿNET, neutrophil extracellular trap.