The contribution of Tribbles isoforms in mammals to insulin regulation and cancer is complex: recently, TRIB2 has been shown to be an Akt agonist (Hill et al., 2017), and an R107L mutation in TRIB1 that aligns with R141Q in TRIB3 promotes leukemogenesis by enhancing ERK phosphorylation and C/EBPα degradation (Yokoyama et al., 2012). This evidence concerns the gene CEBPA and cancer.