UGT2B28 is a UDP-glucuronosyltransferase enzyme that catalyzes glucuronidation of endogenous steroids and other compounds to facilitate their elimination 1. The enzyme exists as three isoforms (types I-III) generated by alternative splicing from a single gene, with only type I possessing full glucuronidation activity 1. UGT2B28 localizes to the endoplasmic reticulum and perinuclear membrane 1, with tissue expression primarily in liver, breast, adipose tissue, and prostate 2. The gene is subject to common copy number variations (CNVs) affecting 13.5% of Caucasians 3, with deletions increasing esophageal squamous cell carcinoma risk 4. In prostate cancer, UGT2B28 overexpression drives progression through stabilization of the HIP1 adaptor protein, activating AR and EGFR signaling pathways leading to ERK1/2 activation and epithelial-to-mesenchymal transition 5. UGT2B28 expression is elevated in African American prostate cancer patients and regulated by both full-length AR and the splice variant ARv7 6. Tumor overexpression associates with higher Gleason scores, nodal invasion, and increased circulating testosterone and DHT levels 7. Conversely, UGT2B28 deletion significantly reduces levels of glucuronidated steroids and inflammatory mediators 8. These findings establish UGT2B28 as both a prognostic biomarker and therapeutic target in prostate cancer.