Novel functions of inactive rhomboid proteins in immunity and disease

Ramasatyaveni Geesala, Priya D. Issuree, Thorsten Maretzky

Research output: Contribution to journalReview articlepeer-review

20 Scopus citations


iRhoms are related to a family of intramembrane serine proteinases called rhomboids but lack proteolytic activity. In mammals, there are two iRhoms, iRhom1 and iRhom2, which have similar domain structures and overlapping specificities as well as distinctive functions. These catalytically inactive rhomboids are essential regulators for the maturation and trafficking of the disintegrin metalloprotease ADAM17 from the endoplasmic reticulum to the cell surface, and are required for the cleavage and release of a variety of membrane-associated proteins, including the IL-6 receptor, l-selectin, TNF, and EGFR ligands. iRhom2-dependent regulation of ADAM17 function has been recently implicated in the development and progression of several autoimmune diseases including rheumatoid arthritis, lupus nephritis, as well as hemophilic arthropathy. In this review, we discuss our current understanding of iRhom biology, their implications in autoimmune pathologies, and their potential as therapeutic targets.

Original languageEnglish (US)
Pages (from-to)823-835
Number of pages13
JournalJournal of Leukocyte Biology
Issue number4
StatePublished - Oct 1 2019
Externally publishedYes


  • a disintegrin and metalloprotease 17 (ADAM17)
  • epidermal growth factor receptor (EGFR)
  • inactive rhomboid 1 (iRHOM1)
  • inactive rhomboid 2 (iRHOM2)
  • rhomboid 5 homolog 1 (RHBDF1)
  • rhomboid 5 homolog 2 (RHBDF2)
  • tumor necrosis factor (TNF)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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