ARK2N (C18ORF25) is a multifunctional regulator involved in transcription-coupled DNA repair, muscle physiology, and viral defense. Mechanistically, ARK2N functions as part of an ARK2N-CK2 complex that phosphorylates Cockayne syndrome protein B (CSB), enhancing CSB binding to stalled RNA polymerase II and promoting transcription-coupled nucleotide excision repair (TC-NER) 1. ARK2N serves as an AMPK substrate in skeletal muscle, with phosphorylation at S67 regulating exercise-induced signaling and muscle contractile function 2. Mice lacking Ark2n exhibit reduced muscle fiber size, exercise capacity, and calcium handling defects in fast-twitch fibers 3. In humans, ARK2N expression is significantly higher in power athletes and positively correlates with type IIA oxidative fast-twitch muscle fiber proportion 3. The ARK2N rs6507691 T allele predicts high expression and associates with greater fast-twitch fiber cross-sectional area in strength athletes and world-class strength competitors 3. Clinically, Ark2n knockout mice phenocopy Cockayne syndrome, indicating ARK2N's importance in DNA repair 1. Additionally, ARK2N functions in viral immunity through interaction with CK2β and shares functional homology with ARKL1 in regulating transcription 4. These findings position ARK2N as a critical regulator of skeletal muscle performance and genomic stability.