| Summary: | Up-frameshift protein 1 (UPF1) plays the role of a vital controller for transcripts, ready to react in the event of an incorrect translation mechanism. It is well known as one of the key elements involved in mRNA decay pathways and participates in transcript and protein quality control in several different aspects. Firstly, UPF1 specifically degrades premature termination codon (PTC)-containing products in a nonsense-mediated mRNA decay (NMD)-coupled manner. Additionally, UPF1 can potentially act as an E3 ligase and degrade target proteins independently from mRNA decay pathways. Thus, UPF1 protects cells against the accumulation of misfolded polypeptides. However, this multitasking protein may still hide many of its functions and abilities. In this article, we summarize important discoveries in the context of UPF1, its involvement in various cellular pathways, as well as its structural importance and mutational changes related to the emergence of various pathologies and disease states. Even though the state of knowledge about this protein has significantly increased over the years, there are still many intriguing aspects that remain unresolved.
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