In higher eukaryotes, transfer RNAs (tRNAs) with the same anticodon are encoded 
by multiple nuclear genes, and little is known about how mutations in these 
genes affect translation and cellular homeostasis. Similarly, the surveillance 
systems that respond to such defects in higher eukaryotes are not clear. Here, 
we discover that loss of GTPBP2, a novel binding partner of the ribosome 
recycling protein Pelota, in mice with a mutation in a tRNA gene that is 
specifically expressed in the central nervous system causes ribosome stalling 
and widespread neurodegeneration. Our results not only define GTPBP2 as a 
ribosome rescue factor but also unmask the disease potential of mutations in 
nuclear-encoded tRNA genes.