ZSCAN21 is a zinc finger transcription factor that serves as a key regulator of α-synuclein (SNCA) gene expression. The protein functions as a transcriptional activator that directly binds to regulatory sequences within SNCA intron 1, stimulating α-synuclein transcription in neuronal cells 12. Mechanistically, ZSCAN21 is regulated through a ubiquitin-proteasome pathway involving E3 ligases TRIM17 and TRIM41, where TRIM17 stabilizes ZSCAN21 by preventing its TRIM41-mediated degradation 3. In disease contexts, ZSCAN21 plays a pathogenic role in Parkinson's disease by mediating neurotoxin-induced α-synuclein upregulation, as demonstrated in MPTP mouse models and cellular studies where ZSCAN21 knockdown prevents both α-synuclein induction and dopaminergic neuronal death 4. The protein also exhibits counter-regulatory effects on synuclein expression, repressing α-synuclein while simultaneously increasing β-synuclein expression, which may reduce α-synuclein aggregation 5. Rare variants in ZSCAN21 have been identified in familial Parkinson's disease patients, with some variants resulting in protein stabilization 36. Additionally, ZSCAN21 functions as a reader of DNA modifications, particularly 5-formylcytosine, suggesting broader epigenetic regulatory roles 7.