Table 2.

Genes involved in the pathogenesis of GPP with description of related proteins encoded and their functions.

Gene Involved	Protein Encoded	Main Functions of the Protein
IL-36RN	IL-36Ra	Inhibition of the proinflammatory effects of IL-36, competing with the agonistic IL-36 cytokines for the attachment to IL-36R
CARD14	CARD14 (CARMA2) Membrane-associated guanylate kinase scaffolding protein, predominantly expressed in keratinocytes	NF-kB and MAPK activation through the formation of a signaling complex with BCL10 and MALT1
AP1S3	σ1C subunit of the AP-1 complex	AP-1 complex is involved in clathrin-mediated vesicular trafficking between the trans-Golgi and the endosomes, autophagosome formation, Toll-like receptor homeostasis and keratinocyte autophagy
MPO	Myeloperoxidase Cationic heme-containing enzyme found in neutrophil azurophil granules	Essential to the antimicrobial activity of neutrophils, it is involved in reactive oxygen species production and phagocytosis, as well as in the generation of neutrophil extracellular traps
SERPINA3	Serpin A3 Serine protease inhibitor	Interaction with the neutrophil protease cathepsin G and other proteases to inhibit their activity
TNIP1	Tumor necrosis factor-alpha induced protein 3 interacting protein 1	Interaction with zinc finger protein A20 to inhibit NF-κB signalling (other targets include the RARs-α and -γ, and peroxisome proliferator-activated receptors)

Information extracted from References [1,69,96,97,98,99,100] AP-1: adaptor protein complex 1; AP1S3: adaptor related protein complex 1 subunit sigma 3; BCL10: B-cell lymphoma/leukemia 10; CARD14: caspase recruitment domain-containing protein 14; GPP: generalized pustular psoriasis; IL: interleukin; IL-36R: interleukin-36 receptor; IL-36Ra: interleukin-36 receptor antagonist; MALT1: mucosa-associated lymphoid tissue lymphoma translocation protein 1; MAPK: mitogen-associated protein kinase; NF-κB: nuclear factor-κB; RAR: retinoic acid receptor.