UNC93B1 is a transmembrane protein that serves as a critical regulator of nucleic acid-sensing Toll-like receptor (TLR) signaling, particularly TLRs 3, 7, 8, and 9 1. The protein facilitates the transport of these TLRs from the endoplasmic reticulum to endolysosomes, where they can engage pathogen nucleotides and activate immune signaling cascades 1. UNC93B1 physically associates with TLR8 and is essential for TLR8-mediated signaling, with different modes of regulation for each TLR subtype 1. Beyond TLR regulation, UNC93B1 also attenuates the cGAS-STING signaling pathway by targeting STING for autophagy-lysosome degradation 2. Clinically, UNC93B1 variants are associated with monogenic autoimmune diseases. Multiple studies have identified gain-of-function mutations causing systemic lupus erythematosus and chilblain lupus through enhanced TLR7/8 signaling 345. These mutations lead to hyperactive TLR7/8 responses, increased type I interferon production, and constitutive inflammatory signaling 4. The protein's role in controlling TLR7 turnover through interaction with the BORC complex and Arl8b is crucial for preventing pathological autoimmune responses 6. UNC93B1 dysfunction represents a key mechanism underlying TLR7-dependent autoimmunity in humans.