Disrupted endosomal degradation leads to aberrant TLR7 signaling, providing a molecular basis for lupus-like autoimmunity in humans.348 Recently, Olivia Majer’ team also identified another novel regulatory mechanism that restricts TLR9 activation to endosomal compartments.349 LR9 signaling is regulated through endosome-specific dissociation from UNC93B1, a prerequisite for ligand engagement and downstream activation. Here, TLR9 is linked to Autoimmunity.