TAF1C (TATA-box binding protein associated factor, RNA polymerase I subunit C) is a core component of the SL1/TIF-IB transcription factor complex essential for RNA polymerase I-dependent ribosomal RNA (rRNA) synthesis 1. TAF1C functions by facilitating pre-initiation complex (PIC) assembly at rDNA promoters and recruiting RNA polymerase I through interaction with RRN3, while stabilizing the nucleolar transcription factor UBTF [UniProt]. The gene is located on chromosome 16 as a single-copy locus with alternative transcription patterns 1. Disease relevance has emerged across multiple conditions. TAF1C frameshift mutations occur in 8.8-10.1% of microsatellite-instable gastric and colorectal cancers, with intratumoural heterogeneity detected in 18.8% of colorectal cases 2. Homozygous missense variants cause severe early-onset neurological phenotypes featuring global developmental delay, seizures, cerebral atrophy, and impaired ribosome biogenesis 3. A novel missense variant (p.Ser589Leu) causes neurodevelopmental regression through disrupted nucleolar localization and nucleoplasmic aggregation rather than expression loss 4. TAF1C expression is significantly elevated in type 2 diabetes mellitus, suggesting increased protein synthesis 5. Additionally, TAF1C emerges as a histone modification-related prognostic marker in prostate cancer 6, and exhibits altered expression in PTSD-associated glucocorticoid signaling pathways 7. These findings establish TAF1C as a critical regulator of nucleolar function with broad implications for cancer, neurodegeneration, and metabolic disease.