SCAF1 is a serine/arginine-rich pre-mRNA splicing factor that interacts with the C-terminal domain of RNA polymerase II to regulate splicing and transcription. The protein functions as a supercomplex assembly factor in mitochondria, where it promotes the assembly of respiratory chain supercomplexes and enhances oxidative phosphorylation-dependent ATP production through the PERK-eIF2α signaling axis. SCAF1 has emerged as a moderate-risk autism spectrum disorder gene. A large exome study of 42,607 autism cases identified SCAF1 among five newly discovered risk genes associated with the disorder, specifically through rare loss-of-function variants 1. Autistic individuals carrying loss-of-function variants in SCAF1 and three other moderate-risk genes showed less cognitive impairment than those with variants in highly penetrant autism genes, suggesting a milder phenotype. SCAF1 has also been implicated in cancer biology. The gene is overexpressed in aggressive ovarian and breast cancers and is being investigated as a cancer biomarker. Recent in vivo CRISPR screens identified SCAF1 as a pancreatic cancer driver gene, with alterations observed in 31% of pancreatic cancer patients 2. Loss of SCAF1 increases sensitivity to PARP inhibition and gemcitabine, indicating potential therapeutic relevance. Additionally, SOX13-mediated upregulation of SCAF1 promotes ferroptosis resistance in gastric cancer; targeting this pathway with zanamivir shows promise for overcoming therapeutic resistance 3.