UXT, also known as ubiquitously expressed prefoldin like chaperone and Androgen Receptor Trapped clone-27 (ART-27), is a small chaperone-like protein. It plays crucial roles in multiple biological processes. UXT is involved in regulating autophagy, cell death, immunity, and transcription, and is associated with pathways like CGAS-STING1 signaling, NF-κB, and others. Its normal function is important for maintaining immune homeostasis, cell metabolism, and tissue integrity [1,2,3].

In DNA-virus infected mouse models and the TMPD-induced murine lupus model, UXT was shown to attenuate the CGAS-STING1 signaling by promoting autophagic degradation of STING1, thus maintaining immune homeostasis [1]. In Sertoli cell-specific Uxt conditional knockout (CKO) mice, deletion of Uxt led to smaller testis size, loss of germ cells, and reduced transcription of genes involved in the tight junctions of the blood-testis barrier, indicating its role in maintaining BTB integrity [4]. Mice deficient in UXT exhibited retinitis pigmentosa-like features with enhanced autophagic flux in the retina, suggesting UXT's role in preventing retinal degeneration by suppressing autophagy [5]. Prostate-specific Uxt knockout (KO) mice developed a hyperplastic phenotype and PIN, and UXT depletion in prostate cancer cells increased retroelements expression, DNA damage, and retrotransposition activity, showing that loss of UXT is an early event in prostate cancer progression [6].

In conclusion, UXT is essential for maintaining autophagy balance, immune homeostasis, and tissue integrity. Studies using Uxt KO/CKO mouse models have revealed its significant roles in diseases such as autoimmune diseases, retinal degenerative diseases, and prostate cancer, providing important insights into the underlying mechanisms and potential therapeutic targets for these diseases.