Trib2 exemplifies this enigma; while reduced Trib2 levels accelerate NOTCH1-driven T-cell acute lymphoblastic leukemia (T-ALL) [10,11,12,13], increased Trib2 levels result in the degradation of the C/EBPα p42 isoform and increased phosphorylation of ERK leading to hematopoietic cell proliferation and leukemia pathologies [14,15,16,17]. The gene discussed is TRIB2; the disease is leukemia.