UBE2J1 is an endoplasmic reticulum-anchored ubiquitin-conjugating enzyme that mediates polyubiquitination and degradation of multiple protein substrates. As a component of the HRD1 ERAD complex, it facilitates ER-associated degradation of misfolded proteins, including MHC class I heavy chains 1 and participates in endolysosomal trafficking through interaction with the E3 ligase RNF26 2. During ER stress, UBE2J1 undergoes phosphorylation-dependent degradation that is essential for cellular recovery 3. In viral infection, UBE2J1 negatively regulates innate immunity by mediating Lys-48-linked ubiquitination of the transcription factor IRF3, thereby suppressing type I interferon expression and promoting dengue virus replication 4. In cancer contexts, UBE2J1 exhibits dual and context-dependent roles: in colorectal cancer, it acts as a tumor suppressor by targeting RPS3 for degradation and inactivating NF-κB signaling 5, whereas in prostate cancer, UBE2J1 controls androgen receptor degradation, and its loss in 5–15% of patients promotes antiandrogen resistance 6. In endometrial and high-grade serous ovarian cancer, elevated UBE2J1 drives progression via PI3K/AKT and JAK2/STAT3/PD-L1 pathways respectively 7 8. These findings identify UBE2J1 as a substrate-selective regulator with therapeutic potential in viral infection and hormone-dependent and immune-modulated malignancies.