ASCC1 is a component of the ASC-1 transcriptional coactivator complex that enhances transactivation by nuclear receptors and transcription factors including NF-κB, SRF, and AP-1. The protein contains two functionally distinct domains: a K-homology domain involved in RNA binding and a two-histidine phosphodiesterase domain 1. ASCC1 plays dual roles in DNA damage repair, functioning within the ASCC complex to respond to alkylation damage and facilitate the disassembly of collided ribosomes during translational quality control 2. Germline mutations in ASCC1 cause spinal muscular atrophy with congenital bone fractures-2 (SMABF2), characterized by prenatal-onset muscle weakness, arthrogryposis, and congenital fractures 3. Disease mechanism studies demonstrate that ASCC1 loss impairs osteoblastogenesis by downregulating the master osteoblast regulator RUNX2 and inhibiting TGF-β/SMAD signaling, while simultaneously promoting adipogenic differentiation in bone marrow mesenchymal cells 4. Beyond inherited disease, germline ASCC1 mutations associate with Barrett esophagus and esophageal adenocarcinoma risk 5, and ASCC1 polymorphisms correlate with osteoporosis and obesity in Korean postmenopausal women 6. Elevated ASCC1 expression in several cancer types correlates with poor survival, though recent evidence suggests ASCC family members inhibit tumor proliferation in lung adenocarcinoma 7.