THAP1 encodes a zinc-binding transcription factor that regulates endothelial cell proliferation and G1/S cell-cycle progression by binding specific DNA sequences and modulating expression of pRB-E2F target genes [UniProt]. It functions as a component of a THAP1/THAP3-HCFC1-OGT complex regulating transcriptional activity [UniProt] and may potentiate apoptosis through serum-withdrawal and TNF-induced pathways [UniProt]. Pathogenic THAP1 variants cause autosomal dominant DYT6 dystonia, characterized by abnormal involuntary muscle contractions 1. THAP1 is the first identified transcription factor implicated in primary dystonia 2, representing a distinct pathogenic mechanism involving transcriptional deregulation 2. Over 56 families carry THAP1 mutations with highly variable penetrance and phenotypes 2. DYT-THAP1 patients exhibit mean age-of-onset of 16.8 years, most commonly affecting the arm, neck, and cranial regions 3. Protein-truncating and THAP domain missense mutations manifest earlier with broader anatomical distribution 3. Transcriptome analysis in human iPSC-derived cortical neurons revealed penetrance-linked alterations in neurotransmitter pathways, extracellular matrix organization, and dopaminergic signaling, particularly DRD4 upregulation in manifesting carriers 4. These insights suggest transcriptional dysregulation during cortical development underlies dystonia pathogenesis.