THAP1, a transcription factor, is essential for timing the inception of myelination during central nervous system (CNS) maturation, through a cell-autonomous role in the oligodendrocyte lineage. It modulates the extracellular matrix (ECM) composition by regulating glycosaminoglycan (GAG) catabolism within oligodendrocyte progenitor cells (OPCs) [2]. THAP1 is also associated with the gene transcription pathway during neurodevelopment and is linked to dystonia [3].

Mutations in THAP1 have been shown to be the cause of DYT6. Different mutation types and locations in the gene are associated with a range of dystonia phenotypes, but clear genotype-phenotype patterns have been difficult to identify [1]. In a study screening THAP1 in dystonia cases, two additional mutations were found, and a correlation between mutation pathogenicity, distribution, and age of onset of dystonia was managed to be found [1]. Also, THAP1 mutations can lead to dysregulation of genes mainly through regulation of SP1 family members, SP1 and SP4, in a cell-type dependent manner [4].

In conclusion, THAP1 plays a crucial role in CNS myelination by regulating ECM degradation in oligodendrocytes. The study of THAP1 mutations through genetic models helps in understanding the pathogenesis of dystonia, a neurological disorder characterized by abnormal involuntary movements or postures. Although clear genotype-phenotype correlations for THAP1-related dystonia are yet to be fully established, research on THAP1 continues to provide insights into the disease mechanism.