Bioinformatic analysis has highlighted the existence of a much wider rhomboid-like family of proteins, many of which, despite showing clear rhomboid homology, lack the hallmark proteolytic residues. These pse'udoproteases' include the iRhoms but also other distantly related proteins. We aim to understand the cellular functions of this wider family.

We have recently discovered that iRhoms can promote the ER associated degradation (ERAD) of EGF receptor ligands, and shown that in Drosophila this provides a mechanism for regulating EGFR activity in the brain. This unexpected mechanism implies that the cellular quality control mechanism is exploited by multicellular organisms to regulate signalling between cells.

We also have evidence that rhomboid-family pseudoproteases participate in human disease mechanisms. We are currently pursuing the medical significance of the rhomboid-like family in mouse models.