RHBDF2 is an inactive rhomboid protein: although it belongs to the peptidase S54 family, it does not exhibit any protease activity on its own. Its recorded role is regulatory. It controls ADAM17, a protease that acts as a sheddase for ligands of the epidermal growth factor (EGF) receptor and for TNF. Through this control, RHBDF2 is linked to sleep, cell survival, proliferation, migration and inflammation.

The protein is found in the endoplasmic reticulum membrane and at the cell membrane. The NCBI Gene summary describes the human gene as predicted to enable protein transporter activity and to act upstream of or within protein localisation to the plasma membrane. It is also predicted to take part in hair follicle morphogenesis, negative regulation of protein secretion and regulation of signal transduction. Researchers studying the RHBDF2 gene often use it as a model for how inactive rhomboid proteins shape the trafficking and activity of membrane proteases.

RHBDF2 is also known as iRhom2, and the symbols RHBDL5, RHBDL6, TOC, TOCG and FLJ22341 appear in the literature. Previous names include rhomboid, veinlet-like 6 (Drosophila) and tylosis with oesophageal cancer, the last reflecting its link to disease. The gene is implicated in palmoplantar keratoderma-esophageal carcinoma syndrome. The mouse ortholog is Rhbdf2, which supports comparative work in rodent models.