TWNK encodes Twinkle, a mitochondrial DNA (mtDNA) helicase that plays a crucial role in mtDNA replication and maintenance 1. The protein functions as part of the core mtDNA replisome alongside DNA polymerase γ and single-stranded DNA binding protein, essential for maintaining mitochondrial genome integrity 2. TWNK is involved in mitochondrial DNA maintenance defects (MDMDs), a group of diseases caused by pathogenic variants in nuclear genes involved in mtDNA synthesis 3. Mutations in TWNK result in impaired mtDNA synthesis leading to quantitative depletion and qualitative defects including multiple mtDNA deletions 3. The gene is associated with several clinical conditions including Perrault syndrome, an autosomal recessive disorder characterized by sensorineural hearing loss, ovarian dysfunction in females, and often neurological abnormalities 14. TWNK variants also cause autosomal dominant progressive external ophthalmoplegia (adPEO) and have been implicated in premature ovarian insufficiency 56. Due to variable mtDNA copy numbers across tissues, TWNK pathogenic variants result in a wide spectrum of clinical manifestations with notable heterogeneity, particularly affecting energy-sensitive organs like the nervous system 1. Recent studies have also identified potential associations with Parkinson's disease 7.