PAF1 is a core component of the PAF1 complex (PAF1C) that plays essential roles in RNA polymerase II-mediated transcription regulation and cellular development 1. The PAF1 complex associates with RNA polymerase II and functions in transcriptional elongation, working both independently and synergistically with other elongation factors 2. Mechanistically, PAF1C displaces the negative elongation factor NELF from RNA polymerase II to enable pause release and transcription activation 2. PAF1 also coordinates histone modifications and mRNA processing events as part of its transcriptional regulatory function 1. The complex is crucial for maintaining stem cell pluripotency and self-renewal, with PAF1 specifically regulating expression of key stemness genes like NANOG through interactions with DDX3 and PHF5A 3. In disease contexts, PAF1 has significant clinical relevance as it is upregulated in pancreatic and ovarian cancer stem cells and demonstrates oncogenic transformation capacity 1. Loss-of-function variants in the related PAF1 complex component CTR9 increase myeloid malignancy risk by approximately 10-fold through dysregulation of hematopoietic stem cell self-renewal 4. Additionally, PAF1 maintains nucleolar organization and ribosomal RNA biogenesis by regulating intergenic ribosomal DNA transcription 5, highlighting its broad cellular functions beyond transcriptional elongation.