Innate immune and inflammatory responses are triggered by pathogen or damage activation of Toll-like (TLR) receptors. The MAPK extracellular signal-regulated kinase 1/2 (Erk1/2) contributes to signalling from many receptors, including TLRs, but how Erk1/2 is spatiotemporally recruited for TLR signalling is not known. SCIMP is an immune-specific transmembrane adaptor which regulates TLR signalling and pro-inflammatory responses in macrophages1,2. SCIMP directly binds TLRs through a non-canonical, TIR-non-TIR interaction, scaffolding the Src family kinase, Lyn, for TLR activation and driving the selective production of pro-inflammatory cytokines including IL-6 and IL-12p40. Here, we reveal that SCIMP is a direct scaffold to recruit and activate Erk1/2 for pro-inflammatory signalling downstream of TLR4. Mass spectrometry, affinity pull downs and co-immunoprecipitation in macrophage lysates show that Erk1/2 is a novel binding partner of SCIMP which is recruited in response to TLR4 stimulation. Lattice light sheet live cell imaging shows that SCIMP spatiotemporally recruits Erk2 to TLR4 signalling domains on membrane ruffles and macropinosomes. BMMs from Scimp-/- mice display defective Erk1/2 recruitment to TLR4, reduced activation of transcription factor c-Fos and impaired production of pro-inflammatory cytokines IL-1ß, TNF, IL-6 and IL-12p40 consistent with Erk1/2 inhibition. Thus, we identify a mechanism by which SCIMP recruits Erk1/2 for c-Fos activation in pro-inflammatory TLR signalling in macrophages3. This positions SCIMP as the key scaffold for Erk1/2 kinase recruitment to TLRs in inflammation and infection. SCIMP is genetically associated with human autoimmune and chronic inflammatory diseases including SLE and Alzheimer’s disease, highlighting the SCIMP/Erk/c-Fos axis as a possible therapeutic target.