Congratulations to Dylan whose paper entitled 'Loss-of-function mutations in the dystonia gene THAP1 impair proteasome function by inhibiting PSMB5 expression' was published today in Nature Communications.

Leveraging insight from co-essentiality data generated via the DepMap project, Dylan defines an essential role for the transcription factor THAP1 in proteasome function by virtue of its role in activating the transcription of the PSMB5 gene. Deletion of THAP1 results in cell death as a result of insufficient PSMB5 protein and impaired proteasome function. Finally, through saturation mutagenesis of the THAP1 protein, Dylan shows that mutations in THAP1 found in patients with the neurological disorder dystonia impair PSMB5 expression, suggesting that dysregulated proteasome function could contribute to disease pathogenesis.

The paper is available online at
https://www.nature.com/articles/s41467-025-56782-1.