text: 3′-UTR mutations can be very consequential because one alteration can be responsible for the altered expression of many genes. Transcriptionally, a mutation may affect only the allele and genes that are physically linked. However, since 3′-UTR binding proteins also function in the processing and nuclear export of mRNA, a mutation can also affect other unrelated genes. Dysregulation of ARE-binding proteins (AUBPs) due to mutations in AU-rich regions can lead to diseases including tumorigenesis (cancer), hematopoietic malignancies, leukemogenesis, and developmental delay/autism spectrum disorders. An expanded number of trinucleotide (CTG) repeats in the 3’-UTR of the dystrophia myotonica protein kinase (DMPK) gene causes myotonic dystrophy. Retro-transposal 3-kilobase insertion of tandem repeat sequences within the 3′-UTR of fukutin protein is linked to Fukuyama-type congenital muscular dystrophy. Elements in the 3′-UTR have also been linked to human acute myeloid leukemia, alpha-thalassemia, neuroblastoma, Keratinopathy, Aniridia, IPEX syndrome, and congenital heart defects. The few UTR-mediated diseases identified only hint at the countless links yet to be discovered.