SCAF8 (SR-related CTD associated factor 8) is an mRNA anti-terminator protein that prevents premature transcription termination during RNA polymerase II (RNAPII) transcription. SCAF8 functions by binding to the phosphorylated C-terminal domain (CTD) of RNAPII and subsequently binding nascent RNA upstream of early polyadenylation sites to suppress their use 1. This mechanism prevents accumulation of non-functional truncated proteins lacking essential domains. SCAF8 works redundantly with its paralog SCAF4 to suppress early mRNA termination, while also functioning independently as an RNAPII elongation factor 1. Beyond its canonical termination role, SCAF8 modulates alternative splicing by directly driving exon inclusion across hundreds of endogenous genes 2. Recent evidence shows SCAF8 abundance is kinase-dependent, with CDK7 inhibition causing nuclear depletion of SCAF8 and triggering widespread 3' end readthrough transcription 3. The protein contains a CTD-interacting domain (CID) that specifically recognizes phosphorylated RNAPII CTD sequences, enabling stage-specific transcriptional control 4. Clinically, SCAF8 variants are associated with IgA nephropathy susceptibility, suggesting roles in immune regulation 5. Loss of SCAF8 expression is lethal in human cells due to its essential role in coordinating transcription elongation and termination.