WDR82 is a regulatory component of the SET1/COMPASS complex that facilitates histone H3 lysine-4 methylation (H3K4me3) at transcriptional start sites of active genes 12. It recruits SETD1A/B methyltransferases to RNA polymerase II through interaction with the phosphorylated CTD of POLR2A 3. Beyond histone methylation, WDR82 serves dual roles in transcriptional regulation: it is part of the PNUTS-PP1 phosphatase complex that promotes RNA polymerase II pause-release and transcription elongation 4, and it forms the restrictor complex with ZC3H4 to suppress processive transcription and terminate lncRNA transcription through inefficient splicing checkpoints 56. The restrictor complex recruits PP1/PNUTS to terminate extragenic transcription by dephosphorylating RNA Pol II CTD Ser5 phosphorylation 7. Clinically, WDR82 expression correlates with colorectal cancer prognosis; decreased WDR82 associates with lymph node and liver metastasis and reduced overall survival 8. WDR82 carbonylation impairs H3K4me3 deposition and glucose metabolism in offspring exposed to maternal high-fat diet, reversible through maternal exercise 9. In multiple myeloma, WDR82 scaffolds c-MYC interactions to promote lipogenic gene expression 10.