ASCC2 is a ubiquitin-binding protein that functions in two major cellular processes: DNA repair and ribosome quality control. In DNA repair, ASCC2 serves as a component of the ASCC complex and recognizes Lys-63-linked polyubiquitin chains at sites of DNA alkylation damage, recruiting ASCC3 and ALKBH3 to facilitate repair 1. The pathway is initiated when aberrant RNA methylation triggers E3 ligase RNF113A to polyubiquitylate proteins at damaged sites 2. ASCC2 also plays a critical role during replication stress, where its ubiquitin-binding activity enables ASCC3 recruitment to stalled replication forks, promoting fork reversal and ATR activation 3. In ribosome quality control, ASCC2 binds K63-linked polyubiquitinated RPS20 (uS10) marked by ZNF598 on collided ribosomes, promoting recruitment of the RQT complex and enabling ASCC3-mediated ribosome disassembly 4. Cancer-associated mutations in ASCC2 reduce its interaction affinity with ASCC3 5, potentially impairing both repair and quality control functions. In lung adenocarcinoma, elevated ASCC2 expression correlates with altered immune cell infiltration and impacts tumor progression 6.