UNC93B1

UNC93B1 is a gene in humans that encodes a transmembrane protein called UNC93B1. This protein plays a crucial role in the innate immune system, specifically in the trafficking and signaling of Toll-like receptors (TLRs).

UNC93B1 is localized to the endoplasmic reticulum (ER) and endosomes. It interacts with and stabilizes certain TLRs, including TLR3, TLR7, TLR9, and TLR13 (in mice), preventing their premature activation within the ER. By chaperoning these TLRs, UNC93B1 ensures they are properly transported to endolysosomes, where they encounter their respective ligands (e.g., viral or bacterial nucleic acids) and initiate appropriate immune responses.

Loss of function or mutations in UNC93B1 can lead to severe immune dysregulation and increased susceptibility to infections, particularly herpes simplex encephalitis (HSE). Specifically, certain genetic variants in UNC93B1 can disrupt the proper endosomal trafficking of TLRs, leading to impaired type I interferon responses and increased vulnerability to viral infections.

Furthermore, UNC93B1 has been implicated in autoimmune diseases. The protein’s role in TLR signaling makes it a potential target for therapeutic interventions aimed at modulating immune responses in both infectious and autoimmune contexts. Research continues to explore the specific mechanisms by which UNC93B1 regulates TLR signaling and its contribution to various disease states.