Table 2.

The disease conditions and the physiological effects of loss of function of either iRhom1, iRhom2 in mouse and human tissues, together with the relevant clients.

disease	gene	phenotypic readout	client
breast cancer	iRhom1	metastasis, poor response to chemotherapy, reduced survival [17]	reduced EGFR activation
colorectal cancer	iRhom1	reduced cell proliferation, migration and invasiveness of tumor [54]	components of Wnt-β catenin signalling
tylosis with oesophageal cancer (TOC)	iRhom2	(i) palmoplantar hyperkeratosis, increased risk of oesophageal cancer (ii) adenoma formation and decreased survival (iii) complete hair loss of mice at birth (iv) increased wound healing [31–33,35,55]	EGFR ligands
gastric cancer-associated fibroblasts	iRhom2	diffuse type gastric ulcers [48]	TGF-β1,ADAM17
inflammatory arthritis		less joint swelling, lowered synovial inflammation, cartilage erosion [56]	n.a.
renal dysfunction	iRhom2	significant protection against tissue inflammation, kidney damage [57]	reduced ADAM17, EGFR
haemophilic arthropathy (HA)	iRhom2	reduction in osteopaenia, synovial inflammation [58]	n.a.
hepatic steatosis	iRhom2	reduced inflammatory cytokines [53]	ADAM17, TNF-α
acute lung injury after intestinal ischaemia-reperfusion	iRhom2	reduction in apoptosis [59]	ADAM17, TNF-α
Listeria monocytogenes infection	iRhom2	(i) increase in granulomas in liver (ii) rapid death post infection [14]	n.a.
HSV-1 infection	iRhom2	defective innate immune response to DNA virus [18]	STING
RNA virus infections (Sendia, VSV)	iRhom2	(i) quicker mortality (ii) increased immune cell infiltration and damage to lungs [20]	VISA
heart diseases	iRhom1 & iRhom2	(i) cardiac infarction (ii) formation of thrombosis [60,61]	n.a.
neurological disease	iRhom2	Alzheimer's (speculated) [49,50]	n.a.