Toll-Like Receptors (TLRs) play critical roles in the early innate immune response to invading pathogens by sensing microorganisms; a number of accessory molecules have been shown to assist microbial recognition by TLRs. In a recent paper in Cell Research, Yang et al. demonstrate that Mex3B is associated with TLR3 in the endosomes and promotes dsRNA binding and proteolytic processing of TLR3, suggesting that Mex3B acts as a coreceptor of TLR3 in response to dsRNA.