The ubiquitin-proteasome system is essential to eukaryotic life through the regulation of protein degradation, and Ubiquilins (UBQLNs) facilitate degradation of a poorly defined subset of ubiquitinated proteins. Since their discovery, multiple UBQLNs have been implicated in cancer and neurodegenerative disease. In particular, mutations in UBQLN2, which is highly expressed in neurons and muscle, were found to cause ALS. We found that UBQLN2 regulates the degradation of a unique, retrotransposon-derived protein called PEG10. PEG10 is necessary for placental development but is elevated in neurological diseases, including Angelman's Syndrome and ALS. We seek to understand: 1) Why UBQLN2 specifically selects PEG10 for facilitated degradation 2) How PEG10 contributes to placental function and neurological disease through its virus-like activities and 3) Can we use this knowledge to understand other UBQLN genes, and other retrotransposon-derived genes like PEG10?
