While these metabolic alterations could be secondary consequences of TBL1 effects on proliferative pathways and deserve further attention in future studies, it is still tempting to speculate that the TBL1 transcriptional co-factor complex defines a conserved “metabolic” checkpoint between non-malignant and cancer cells, controlling essential nodes in metabolic pathways under both homeostatic (fasting-feeding cycles) and malignant conditions. This evidence concerns the gene TBL1Y and cancer.