DENR and nervous system disorder: Whereas it will be informative to determine whether both substitutions could disrupt the role for DENR in other aspects of mRNA translation, including ribosome recycling and termination-dependent and -independent re-initiation of viral mRNAs (Skabkin et al., 2010, Zinoviev et al., 2015), our current findings nonetheless provide critical mechanistic insight into the pathological consequences of DENR substitution mutations in mRNA translation and link its altered molecular functions to human neurological disease.