SCAF1 (SR-related CTD associated factor 1) is a multifunctional protein that plays critical roles in transcriptional regulation and mitochondrial bioenergetics. As a member of the SR superfamily of pre-mRNA splicing factors, SCAF1 interacts with the C-terminal domain of RNA polymerase II and functions as a critical activator of RNA polymerase II elongation and global transcription 12. Mechanistically, SCAF1 depletion leads to RNA polymerase II stalling at GC-rich regions within gene bodies, resulting in decreased RNA synthesis and increased proteasomal degradation of stalled polymerase complexes 2. Beyond transcriptional regulation, SCAF1 serves as a supercomplex assembly factor (also known as COX7A2L) that promotes formation of mitochondrial respiratory chain supercomplexes, enhancing oxidative phosphorylation and ATP production 34. The protein is upregulated by the PERK-eIF2α-ATF4 pathway during ER stress and nutrient deprivation 3. Clinically, SCAF1 has significant disease relevance as a moderate-risk gene for autism spectrum disorders 5, a potential tumor suppressor in pancreatic cancer 6, and shows altered expression in focal segmental glomerulosclerosis 7. Loss of SCAF1 affects cellular metabolism by increasing glutamine dependency and promoting anabolic pathways 4, making it a potential therapeutic target in metabolic diseases and cancer.