Velasco Díez, GuillermoLorente Pérez, María Del Mar2026-07-242026-07-242026-07Velasco, G., & Lorente, M. (2026). Tribbles pseudokinases: Fine tuning of cell signaling with implications in metabolism, inflammation and cancer. Current Opinion in Cell Biology, 102, 102673. https://doi.org/10.1016/j.ceb.2026.1026730955-067410.1016/j.ceb.2026.102673https://hdl.handle.net/20.500.14352/138883Work in G Velasco and M Lorente laboratory is supported by Instituto de Salud Carlos III (ISCIII) and confounded by the European Regional Development Fund (ERDF), ‘A way to make Europe’, grant number PI24/00866 integrated into the State Plan for R & D+I 2024–2027, and by the Madrid Region Government Network Program in Biosciences, grant number S2022/BMD-7434 (ASAP-CM). Tribbles research in our group was funded by the European Commission through the Horizon 2020 European Training Networks program, grant number H2020-MSCA-ITN-308 2016 721532.Within the family of protein kinases there is a subgroup of ‘evolutionarily related members of the total human kinome’ that are devoid (or have very limited) enzymatic activity. These proteins, so-called pseudokinases, play important functions thanks to their capacity to establish regulatory protein–protein interactions. Specifically, this opinion article focuses on a group of pseudokinases called Tribbles. Tribbles (Trbl) was originally discovered in Drosophila, followed by the subsequent identification of their orthologs in mammals (TRIB1, TRIB2, TRIB3, and STK40). Work over the last decades has shown how these proteins contribute to fine-tuning key signaling pathways involved in the regulation of proliferation, differentiation, inflammation and adaptation to nutritional changes. Accordingly, dysregulation of Tribbles proteins (TRIBs) contributes to the establishment and progression of insulin resistance, obesity, type II diabetes, atherosclerosis and cancer. Here, we will discuss some of the mechanisms by which Tribbles pseudokinases carry out their functions and the crucial importance of cell context in defining the precise role played by each of the TRIBs, with emphasis on TRIB1 and TRIB3, under different physiopathological situations.engAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/review article1879-0410https://doi.org/10.1016/j.ceb.2026.102673https://www.sciencedirect.com/science/article/pii/S095506742600061X?via%3Dihubopen access577.21577.12616-006616-002Biología celular (Biología)Biología molecular (Biología)OncologíaInmunología2407 Biología Celular2302.21 Biología Molecular3201.01 Oncología2412 Inmunología2302.09 Enzimología