The ability to translate genetic information into functional proteins is considered a landmark in evolution. ribosome biogenesis and protein synthesis at the crossroads of pathological settings particularly cancer exposing a set of novel cellular checkpoints. Moreover it is also becoming obvious that mTOR signaling which regulates an array of anabolic processes including ribosome biogenesis is usually often exploited by malignancy cells to sustain proliferation through the upregulation of global protein synthesis. The use of pharmacological brokers that interfere with ribosome biogenesis and mTOR signaling has proven to be an effective strategy to control malignancy development clinically. Here we discuss the most recent findings concerning the underlying mechanisms by which mTOR signaling controls ribosome production and the potential impact of ribosome bio-genesis in tumor development. This article is usually part TMCB of a Special Issue entitled: Translation and Malignancy. . Shortly after the mammalian homologue mammalian Target of Rapamycin (mTOR) was purified and cloned in four other laboratories [20-23]. Although mTOR belongs to the phosphatidylinositol 3-kinase-related protein kinase subsequent studies in mammalian systems showed that mTOR was a protein rather than a lipid kinase [24 25 Since then considerable efforts have been invested in understanding the functions mechanisms and contexts where this pivotal regulator of cellular metabolism exerts its effects. Many proteins have been found associated with mTOR and unique components define two mTOR protein complexes mTOR Complex1 (mTORC1) and mTORC2 . Common partners are found in both complexes including mammalian lethal with SEC13 protein 8 (mLST8)  and the inhibitory protein DEP domain-containing mTOR-interacting protein (DEPTOR)  whereas specific components differentiate the two complexes in terms of target specificity and sensitivity to external stimuli such as Regulatory-associated protein of mTOR (RAPTOR) and Proline-rich AKT1 substrate 1 (PRAS40) in the case of mTORC1 or Rapamycin-insensitive companion of mammalian target of rapamycin (RICTOR) and mSIN-1 in the case of mTORC2 . Although it has been argued that rapamycin is usually selective for mTORC1 and not mTORC2 recent studies provide evidence that it can also bind mTORC2 when combined with one of the novel mTOR ATP-site competitive inhibitors . The number of signaling pathways branching from mTORC1 and mTORC2 the cascade of events which control both complexes and the feedback mechanisms between effectors have TMCB revealed an intricate network of regulatory events . Seminal CD340 studies first in yeast and drosophila [31 32 then in mice have exhibited that mTOR is essential for cell growth and proliferation as mTOR knockout mouse embryos fail to progress beyond the early step TMCB of pre-implantation due to a defect in blastocyst inner-cell-mass proliferation and tropho-blast differentiation [33 34 Importantly rapamycin administration TMCB to wild type blastocysts partially recapitulates the phenotype of mTOR?/? embryos which suggested that loss of mTORC1 might be the culprit . This was also supported by the effects of RAPTOR deletion which recapitulated the phenotype of mTOR loss in mouse development . The time at which mTORC1 comes into play TMCB during mouse development reflects a specific energetic need of the blastocyst which at the early actions of embryogenesis is dependent on amino acids as an energy source. Of notice genetic ablation of RICTOR in the mouse unraveled a differential role for mTORC2 which is required at a later stage of gestation as embryos pass away at E10.5. In the same study Guertin et al. decided that this mLST8 although shared by both mTORC1 and mTORC2 complexes has a more profound role in maintaining the functional and physical integrity of mTORC2 as confirmed by the finding that have exhibited that mitogen activation prospects to PDCD4 degradation which is usually brought on by S6K1-mediated phosphorylation at serine 67 (S67). Phosphorylation at this site leads to the recruitment of E3-ubiquitin ligase SCFTRCP to PDCD4.