iRhom2: An Emerging Adaptor Regulating Immunity and Disease

Area of Science:

• Molecular biology
• Cellular biology
• Biochemistry

Background:

• The rhomboid family comprises evolutionary conserved intramembrane proteases.
• Inactive rhomboid family members (iRhoms) lack catalytic activity.
• Mammalian iRhom1 and iRhom2 are crucial for the maturation and trafficking of ADAM17.

Purpose of the Study:

• To review the multifaceted roles of iRhom2 in immunity and disease.
• To explore iRhom2 functions both dependent and independent of ADAM17 regulation.
• To highlight iRhom2's influence on critical cellular signaling pathways.

Main Methods:

• Literature review of existing research on iRhom2.
• Analysis of iRhom2's involvement in ADAM17-dependent signaling.
• Investigation of iRhom2's independent roles in innate immunity and disease.

Main Results:

• iRhom2 significantly impacts ADAM17 activation and substrate specificity, thereby regulating TNFα, EGFR, IL-6, and Notch signaling.
• iRhom2 is implicated in the innate immune response against RNA and DNA viruses.
• iRhom2 influences keratin expression in wound healing and cancer contexts.

Conclusions:

• iRhom2 is a critical regulator of multiple signaling pathways, primarily through its interaction with ADAM17.
• iRhom2 possesses significant biological functions in immunity and disease that extend beyond its regulation of ADAM17.
• Understanding iRhom2's diverse roles is essential for therapeutic strategies in inflammatory diseases, viral infections, and cancer.