SMG-9 is part of a protein kinase complex, SMG1C, which consists of the SMG-1 kinase, SMG-8 and SMG-9. SMG1C mediated phosphorylation of Upf1 triggers nonsense-mediated mRNA decay (NMD), a eukaryotic surveillance pathway that detects and targets for degradation mRNAs harboring premature translation termination codons. Here, we have characterized SMG-9, showing that it comprises an N-terminal 180 residue intrinsically disordered region (IDR) followed by a well-folded C-terminal domain. Both domains are required for SMG-1 binding and the integrity of the SMG1C complex, whereas the C-terminus is sufficient to interact with SMG-8. In addition, we have found that SMG-9 assembles in vivo into SMG-9:SMG-9 and, most likely, SMG-8:SMG-9 complexes that are not constituents of SMG1C. SMG-9 self-association is driven by interactions between the C-terminal domains and surprisingly, some SMG-9 oligomers are completely devoid of SMG-1 and SMG-8. We propose that SMG-9 has biological functions beyond SMG1C, as part of distinct SMG-9-containing complexes. Some of these complexes may function as intermediates potentially regulating SMG1C assembly, tuning the activity of SMG-1 with the NMD machinery. The structural malleability of IDRs could facilitate the transit of SMG-9 through several macromolecular complexes. © 2010 The Author(s). ; Spanish Ministry of Science and Innovation (SAF2008- 00451 to O.L ., SAF2008-00479 to J.T.); ‘Red Temática de Investigación Cooperativa en Cáncer (RTICC)’ from the ‘Instituto de Salud Carlos III’ (RD06/0020/1001 to O.L. and RD06/0020/0011 to J.T.); Autonomous Region of Madrid (CAM S-BIO-0214-2006 to O.L.); Human Frontiers Science Program (RGP39/2008 to O.L.); ‘Consejería de Educación de la Comunidad de Madrid y Fondo Social Europeo’ (to E.A.P.); Japan Society for the Promotion of Science (to A.Y. and S.O.); Japan Science and Technology Corporation (to A.Y. and S.O.); Ministry of Education, Culture, Sports, Science and Technology of Japan (to S.O.); Yokohama Foundation for Advancement of Medical Science (to A.Y.). Funding for open access charge: Spanish Ministry of Science and Innovation