Nucleomethylin (NML), also known as ribosomal RNA-processing protein 8 (RRP8) and human cerebral protein 1 (Hucep-1), is a nucleolar protein (1,2). NML interacts with the histone de-acetylase protein SirT1 and histone methyl-transferase protein SUV39H1 to form the energy- dependent nucleolar silencing complex (eNoSC) that regulates ribosomal RNA (rRNA) transcription in response to changes in the energy state of the cell (2). As energy levels in the cell decrease due to caloric restriction, eNoSC binds to rRNA genes and represses transcription by SirT1-mediated de-acetylation of histones and SUV39H1- mediated methylation of histone H3 on Lys9. NML binds to di-methylated Lys9 of histone H3 and likely functions in the recruitment and spreading of eNoSC along the rRNA genes (2). NML also contains a methyltransferases-like domain, which binds to S-adenosyl-methionine (SAM) and is required for eNoSC function (2). By limiting the transcription of rRNA genes during caloric restriction, eNoSC promotes the restoration of energy balance and protects cells from energy-dependent apoptosis.