ASCC3 is a multifunctional ATPase and 3'-5' DNA helicase with roles in DNA repair, ribosome quality control, and transcriptional regulation. As a component of the ASC-1 complex, ASCC3 functions in alkylated DNA repair by promoting DNA unwinding to generate single-stranded substrates for ALKBH3-mediated processing of alkylated bases 1. ASCC3 is a critical ribosome quality control factor that disassembles collided ribosomes in an ATP-dependent, ZNF598-ubiquitination-dependent manner as part of the ribosome-associated quality control (RQC) pathway 2. During replication stress, ASCC3 is recruited to stalled replication forks via ASCC2 and unwinds DNA to promote fork reversal and ATR activation while antagonizing RAD51-mediated recombination 3. Beyond DNA metabolism, ASCC3 participates in transcriptional regulation through ASC-1 complex-mediated NF-κB, SRF, and AP1 transactivation 4. In cancer contexts, elevated ASCC3 expression promotes non-small cell lung cancer progression by stabilizing STAT3 signaling through CAND1-mediated inhibition of STAT3 ubiquitination, suppressing interferon responses and inducing immunosuppression 5. Conversely, ASCC3 activation ameliorates fragile X syndrome phenotypes by restoring collided ribosome handling in the absence of FMRP 6. ASCC3 dysfunction is associated with intellectual developmental disorder and chr6 hepatitis B susceptibility 7.