biostudies-literatureUnknown136(2)Feng TAndrogen deprivation therapy is the primary treatment for advanced prostate tumors. While initially effective, tumor progression to the therapy-resistant stage is inevitable. Paradoxically, UDP glucuronosyltransferase family 2 member B17 (UGT2B17), the key enzyme responsible for androgen catabolism in prostate tumor cells, is upregulated in therapy-resistant tumors, though its role in tumor progression remains unclear. Here, we demonstrate that UGT2B17 possesses multiple oncogenic functions independent of androgen catabolism. It modulates protein-folding pathways, allowing tumor cells to endure therapy-induced stress. UGT2B17 also regulates transcription associated with cell division and the DNA damage response, enabling unchecked cell proliferation. Targeting the newly identified UGT2B17 The Journal of clinical investigatione196495https://www.ebi.ac.uk/biostudies/studies/S-EPMC12807465biostudies-literatureNoncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression.PMC12807465Levesque EQi JKung SHDong XXie NFazli LWang LJia QLi YHan BLack NAGao LMorova TLacombe LGuillemette CFeng TfalseNoncanonical functions of UGT2B17 promote castration-resistant prostate cancer progression.Androgen deprivation therapy is the primary treatment for advanced prostate tumors. While initially effective, tumor progression to the therapy-resistant stage is inevitable. Paradoxically, UDP glucuronosyltransferase family 2 member B17 (UGT2B17), the key enzyme responsible for androgen catabolism in prostate tumor cells, is upregulated in therapy-resistant tumors, though its role in tumor progression remains unclear. Here, we demonstrate that UGT2B17 possesses multiple oncogenic functions independent of androgen catabolism. It modulates protein-folding pathways, allowing tumor cells to endure therapy-induced stress. UGT2B17 also regulates transcription associated with cell division and the DNA damage response, enabling unchecked cell proliferation. Targeting the newly identified UGT2B17 2026-01-01T00:00:00Z2026 Jan2026-06-10T05:13:29.153Z2026-06-10T03:07:44.122ZS-EPMC128074654134324510.1172/JCI196495