APTX (aprataxin) is a DNA-binding protein and RNA-DNA deadenylase that protects genome integrity by resolving abortive DNA ligation intermediates 1. Its primary function is removing 5'-adenosine monophosphate (AMP) groups from DNA strand breaks generated when DNA ligases fail to complete repair of non-ligatable breaks induced by reactive oxygen species 1. APTX catalyzes this adenylate hydrolysis through a wedge-pivot-cut mechanism, producing 5'-phosphate termini suitable for efficient DNA religation 1. The enzyme functions in single-strand break repair (SSBR) and base excision repair (BER) pathways, where it works with XRCC1 to remove blocking groups at damage sites 2. APTX also participates in double-strand break repair, acting independently of XRCC4 in this pathway 3. Mutations in APTX cause ataxia-oculomotor apraxia 1 (AOA1), a neurodegenerative disorder 1. AOA1 mutations impair APTX through multiple mechanisms: sixteen variants destabilize the protein, one alters catalytic chemistry, and others allosterically disrupt active site conformations 1. APTX deficiency produces secondary CoQ10 deficiency and cerebellar ataxia 4. Critically, APTX functions in both nuclear and mitochondrial compartments; mitochondrial repair is particularly vulnerable to APTX loss, as mtDNA repair cannot compensate for APTX deficiency, leading to accumulation of mitochondrial DNA damage and dysfunction 5.