Toll-like receptors (TLRs) are activated by pathogen or danger signatures for signalling and initiation of innate immune or inflammatory responses. TLR-induced signalling pathways program the release of inflammatory cytokines and other mediators under the influence of signalling adaptors, cross-talk receptors, GTPases, kinases, phospholipids and membrane compartments. As a direct, non-TIR binding partner of TLRs, the transmembrane adaptor SCIMP scaffolds Src kinases that phosphorylate TLRs and drive selective, proinflammatory cytokine outputs. The expression, phosphorylation and trafficking of SCIMP itself are regulated within pathogen-activated environments to orchestrate TLR regulation, coupled with other cell surface proteins. The roles of SCIMP as a member of the transmembrane TRAP adaptor family will be presented along with its potential for regulating inflammation in homeostasis and disease.