Transforming growth factor beta activator LRRC33 (NRROS)

Transforming growth factor beta activator LRRC33 (abbreviated as NRROS) is a leucine-rich repeat-containing transmembrane protein functioning as a specific *milieu molecule* for transforming growth factor beta-1 (TGF-β1). LRRC33 directly binds the latent form of TGF-β1 via both covalent and non-covalent interactions and presents it at the cell membrane in myeloid cells, including macrophages, microglia, and acute myeloid leukemia cells. This presentation enables integrin-dependent activation of TGF-β1, a key immunoregulatory and homeostatic cytokine. Unlike closely related GARP (LRRC32), LRRC33 (NRROS) is highly expressed in myeloid lineages and microglia but not in platelets or T regulatory cells. Although originally described as a negative regulator of reactive oxygen species, this name is now considered misleading by some, as its immunosuppressive functions are largely due to TGF-β1 activation rather than direct enzymatic regulation of ROS. Biallelic mutations or dysfunction of LRRC33 lead to severe inflammatory and neurodegenerative phenotypes due to loss of TGF-β1 activity and immune misregulation. It is a validated protein target for investigating myeloid and neuroimmune system diseases. **Notes**: - LRRC33/NRROS is experimentally established as a TGF-β1 activator in microglia and myeloid cells, not as a classic receptor or enzyme. - No approved drugs or small molecules are characterized as direct interactors or inhibitors/activators of LRRC33/NRROS. - The direct regulation of reactive oxygen species by NRROS is now questioned; its role in ROS suppression is likely downstream of TGF-β1 activation.

Other names

Negative regulator of reactive oxygen speciesLRRC33Leucine-rich repeat-containing protein 33Glycoprotein A repetitions predominant like 1GARPL1SENEBACUNQ3030ELLP3030MGC50789