NRROS is a leucine-rich repeat protein that functions as a critical regulator of TGF-β1 activation in immune cells, particularly microglia and macrophages 1. The protein uniquely anchors latent TGF-β1 on the cell surface through disulfide bond interactions with the latency-associated peptide, enabling integrin-dependent TGF-β1 activation in a localized manner 1. This localized activation prevents spreading of activated TGF-β1 between neighboring immune cells [UniProt]. NRROS also negatively regulates ROS generation and suppresses RANKL-induced NF-κB activation in osteoclasts, thereby inhibiting osteoclast differentiation 2. Additionally, NRROS indirectly modulates TLR-mediated inflammatory responses through its role in TGF-β1 signaling 3. Biallelic NRROS variants cause a severe neurodegenerative microgliopathy characterized by infantile-onset seizures (often drug-resistant), progressive developmental regression, intracranial calcifications, and white matter abnormalities 41. Clinical onset typically occurs within the first year of life, with median survival around 36 months 4. Disease-causing variants impair NRROS's ability to anchor latent TGF-β1 at the cell surface, resulting in defective TGF-β1 activation 1. Common NRROS variants are also associated with vitiligo susceptibility in multiple populations 56.