Rhomboid-like proteins: from molecular principles to pathophysiological significance

Cells use a family of proteins called rhomboid-likes to cut and control other proteins embedded in their membranes, but scientists still do not understand how most of these molecular scissors work or what they do in the human body. This matters because rhomboid-like proteins are involved in inflammation, growth factor signalling, and tumour growth—yet the specific targets they act on remain largely unknown. Without knowing which proteins they cut or bind, researchers cannot tell whether a given rhomboid-like protein is a cause of disease or a bystander. The team has already shown that one inactive member, iRhom, regulates tumour growth, but the underlying mechanisms are unclear. The research aims to solve this by combining structural biology and biochemistry to reveal how rhomboid-like domains recognise their targets, and by developing systematic methods to identify those targets in living cells. If successful, this work will map the molecular roles of rhomboid-like proteins in mammals and identify which ones are useful therapeutic targets for diseases such as cancer and chronic inflammation. This is fundamental science. There is no immediate practical application, but understanding how these membrane-embedded machines work could eventually lead to drugs that block or mimic their activity—much as basic research on other proteases led to HIV drugs and blood pressure medications.