Nonsense-mediated mRNA decay (NMD) protects many heterozygous carriers of defective genes that encode pre-mature termination codons (PTCs) from manifesting dominantly inherited disorders that would result if the encoded truncated proteins were expressed (PMID: 20795950, 21550797). It is very important for cells to remove PTC-containing mRNAs, whether they are somatically acquired or genetically inherited, because the encoded truncated proteins have the potential to manifest dominant-negative or gain-of-function activities. Thus, NMD plays a key protective role in a long list of human diseases that are due to frameshift or nonsense mutations and result in the premature termination of mRNA translation, including β⁰-thalassemia, cystic fibrosis, Duchenne muscular dystrophy and a number of cancers that involve PTCs within, for example, BRCA1 or WT1 tumor suppressor mRNAs (PMID: 20795950, 21550797).

In human the SMG5-SMG7 mediated NMD leads to deadenylation and/or decapping followed, repectively, by exosome-mediated 3'-to-5' and XRN1-mediated 5'-to-3' exonuclolytic activities. (PMID: 21550797)