GTF3C3 encodes a key DNA-binding component of transcription factor IIIC (TFIIIC), which is essential for RNA polymerase III-mediated transcription of non-coding RNAs including tRNAs and 5S rRNA 1. As an integral subunit of the TFIIIC2 complex, GTF3C3 directly binds tRNA and virus-associated RNA promoters to facilitate transcription initiation 2. Biallelic GTF3C3 variants cause autosomal recessive neurodevelopmental disorder characterized by intellectual disability, microcephaly, distinctive dysmorphic facies, seizures, and cerebellar/frontal lobe anomalies 13. Pathogenic missense variants disrupt intra- and intermolecular protein interactions, resulting in loss-of-function effects confirmed by RNA polymerase III reporter assays 3. Some variants introduce cryptic splice sites causing mRNA missplicing 3. Animal models demonstrate that GTF3C3 loss recapitulates human clinical features including seizure susceptibility and motor impairments, with reduced RNA polymerase III target gene expression 13. The discovery of GTF3C3 as a disease gene expands understanding of TFIIIC-linked neurodevelopmental pathologies and highlights the critical role of RNA polymerase III transcription in normal brain development.