BACKGROUND: Nonsense-mediated mRNA decay (NMD) is a post-transcriptional RNA 
surveillance process that facilitates the recognition and destruction of mRNAs 
bearing premature terminations codons (PTCs). Such PTC-containing (PTC+) mRNAs 
may arise from different processes, including erroneous processing and 
expression of pseudogenes, but also from more regulated events such as 
alternative splicing coupled NMD (AS-NMD). Thus, the NMD pathway serves both as 
a silencer of genomic noise and a regulator of gene expression. Given the early 
embryonic lethality in NMD deficient mice, uncovering the full regulatory 
potential of the NMD pathway in mammals will require the functional assessment 
of NMD in different tissues.
METHODOLOGY/PRINCIPAL FINDINGS: Here we use mouse genetics to address the role 
of UPF2, a core NMD component, in the development, function and regeneration of 
the liver. We find that loss of NMD during fetal liver development is 
incompatible with postnatal life due to failure of terminal differentiation. 
Moreover, deletion of Upf2 in the adult liver results in hepatosteatosis and 
disruption of liver homeostasis. Finally, NMD was found to be absolutely 
required for liver regeneration.
CONCLUSION/SIGNIFICANCE: Collectively, our data demonstrate the critical role of 
the NMD pathway in liver development, function and regeneration and highlights 
the importance of NMD for mammalian biology.