We now show that the metabolic and tumor suppressor effects of RARRES1 are mediated by its inhibition of CCP2 catalyzed tubulin deglutamylation, which in turn regulates mitochondrial bioenergetics and subsequently alters energy homeostasis by modulating the function of the mitochondrial voltage-dependent anion channel 1 (VDAC1). This evidence concerns the gene RARRES1 and neoplasm.