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Alliance"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:p>The metalloprotease ADAM17 is a sheddase of key molecules, including TNF and epidermal growth factor receptor ligands. ADAM17 exists within an assemblage, the \u201csheddase complex,\u201d containing a rhomboid pseudoprotease (iRhom1 or iRhom2). iRhoms control multiple aspects of ADAM17 biology. The FERM domain\u2013containing protein iTAP\/Frmd8 is an iRhom-binding protein that prevents the precocious shunting of ADAM17 and iRhom2 to lysosomes and their consequent degradation. As pathophysiological role(s) of iTAP\/Frmd8 have not been addressed, we characterized the impact of iTAP\/Frmd8 loss on ADAM17-associated phenotypes in mice. We show that iTAP\/Frmd8 KO mice exhibit defects in inflammatory and intestinal epithelial barrier repair functions, but not the collateral defects associated with global ADAM17 loss. 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