Further compound optimisation is required to elaborate on leads for both TRIB1 and TRIB2, but knowing that TRIB1 can adopt SLE-in and SLE-out conformations analogous to DFG-in and DFG-out conformations of conventional kinases is highly relevant to future efforts to pharmacologically target Tribbles proteins. Here, TRIB2 is linked to systemic lupus erythematosus.