TAF1 (TATA-box binding protein associated factor 1) is the largest component and core scaffold of the TFIID basal transcription factor complex, which is essential for RNA polymerase II-dependent transcription initiation 1. As part of TFIID, TAF1 nucleates complex assembly and forms a promoter DNA-binding subcomplex with TAF7 and TAF2 12. TAF1 possesses dual kinase and histone acetyltransferase activities, phosphorylating transcription factors including TP53 at Thr-55 and GTF2A1/GTF2F1, while acetylating histones H3 and H4 23. The protein is essential for G1 cell cycle progression 4. Mechanistically, circDYM can bind TAF1 to suppress downstream target gene expression and neuroinflammation 5. Pathogenic TAF1 variants cause X-linked intellectual developmental disorder with syndromic features (TAF1/MRXS33 syndrome), characterized by early-onset hypotonia, facial dysmorphia, developmental delay, autism spectrum disorder, seizures, hearing loss, and cardiac malformations 67. TAF1 dysfunction is also associated with X-linked dystonia-parkinsonism (DYT3) 89. The X-chromosome X (Xq13.1) and extensive phenotypic pleiotropy complicate pathogenicity determination for inherited missense variants 106.