In innate immunity, danger signals such as Gram-negative bacterial lipopolysaccharide (LPS) initiate host inflammatory responses by engaging members of the Toll-like Receptor (TLR) family. TLR4 activates inflammatory responses through recruitment of a small number of TIR-domain containing adaptor proteins that shape signalling and transcriptional responses. We hypothesized that additional adaptors may be necessary to diversify cytokine outputs. Here, using GST pull-downs and mass spectrometry, we identified SCIMP as a novel binding partner for TLR41. SCIMP is a transmembrane adaptor and belongs to a member of the pTRAP family; it is a non-TIR domain containing protein but we identified that a specific region at C terminus of SCIMP binds to the TIR domain of TLR4 in an LPS-induced and novel manner. SCIMP and TLR4 are co-located in lipid raft domains on filopodia and surface ruffles of activated macrophages. SCIMP scaffolds Lyn kinase and is responsible for Lyn-dependent tyrosine phosphorylation of TLR4. SCIMP silencing or knockout and functional studies show that SCIMP induces pro-inflammatory signalling and a surprisingly specific output of pro-inflammatory cytokines, confined to IL-6 and IL-12p40. Phosphorylation deficient mutations in SCIMP that abrogate TLR4 binding also prevent LPS-inducible production of SCIMP-dependent cytokines. Using newly developed phosphorylation probes2 we can show that SCIMP is phosphorylated in response to multiple TLR ligands, via different effectors and with different kinetics; SCIMP binds to multiple TLRs suggesting it is a universal regulator for TLR responses. Our studies implicate SCIMP as the adaptor for TLR tyrosine phosphorylation and reveal SCIMP as a wholly new proximal adaptor that imparts remarkable specificity in downstream inflammatory cytokine responses.