Key regulator of transforming growth factor beta-1 (TGFB1) specifically required for microglia function in the nervous system (PubMed:29909984). Required for activation of latent TGF-beta-1 in macrophages and microglia: associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGFB1, and regulates integrin-dependent activation of TGF-beta-1 (PubMed:29909984). TGF-beta-1 activation mediated by LRRC33/NRROS is highly localized: there is little spreading of TGF-beta-1 activated from one microglial cell to neighboring microglia, suggesting the existence of localized and selective activation of TGF-beta-1 by LRRC33/NRROS (PubMed:29909984). Indirectly plays a role in Toll-like receptor (TLR) signaling: ability to inhibit TLR-mediated NF-kappa-B activation and cytokine production is probably a consequence of its role in TGF-beta-1 signaling (Probable). Interacts with TGFB1; associates via disulfide bonds with the Latency-associated peptide chain (LAP) regulatory chain of TGFB1, leading to regulate activation of TGF-beta-1 (PubMed:29909984). Interacts (via LRR repeats) with TLR2, TLR3, TLR4, TLR9 and probably other Toll-like receptors (By similarity). Interacts with CYBB/NOX2; the interaction is direct (PubMed:24739962). Mainly expressed in cells of hematopoietic origin, such as in immune organs such as lymph nodes, thymus and spleen (PubMed:24739962, PubMed:29909984). Among leukocytes, expressed at higher level in myeloid cell such as macrophages, neutrophils and dendritic cells (PubMed:24739962). Highly expressed in central nervous system-resident macrophages, including microglia and perivascular macrophages (PubMed:28459434, PubMed:29909984). Down-regulated by IFN-gamma (IFNG), LPS or TNF-alpha in bone marrow-derived macrophages (BMDMs). N-glycosylated. Mice develop paraparesis and neurodegeneration and display reactive microglia caused by defects in TGF-beta-1 signaling (PubMed:29909984). Mice are viable at six-weeks of age and immune organs and leukocyte subsets are not affected (PubMed:24739962). However, significantly increased reactive oxygen species (ROS) production is observed in primary bone marrow-derived macrophages (BMDMs) upon zymosan stimulation (PubMed:24739962). Mice are more susceptible to Toll-like receptor (TLR) ligand challenges: the macrophages and dendritic cells produce more pro-inflammatory cytokines through increased activation of MAPK and NF-kappa-B (PubMed:24550525). By two months of age, mice begin to display neurological symptoms including defects in motor control and strength and die before six months of age (PubMed:28459434, PubMed:29909984). Mice show microglial development defects (PubMed:28459434, PubMed:29909984). Mice develop progressive paraparesis associated with loss of myelin and axons in the spinal cord and brainstem (PubMed:29909984). Belongs to the LRRC32/LRRC33 family. Was initially thought to act as a negative regulator of reactive oxygen species (ROS) that limits ROS production by phagocytes during inflammatory response, thereby playing a role during host defense (PubMed:24739962). However, these results were based on indirect evidences and could not be confirmed by another group (PubMed:29909984). It was later shown to act as a key regulator of transforming growth factor beta-1 (TGFB1) (PubMed:29909984). Truncated N-terminus.