ASCC1 (activating signal cointegrator 1 complex subunit 1) is a multifunctional nuclear protein combining a K-Homology RNA-binding domain with a two-histidine phosphodiesterase domain 1. As a component of the ASC-1 transcriptional coregulator complex, ASCC1 enhances transactivation by NF-κB, SRF, and AP1 transcription factors 2. The ASC-1 complex disassembles collided ribosomes during ribosome-associated quality control in an ATP-dependent, ubiquitination-dependent manner 3. ASCC1 also participates in DNA alkylation damage repair as part of the ASCC-ALKBH3 complex 1. Pathogenic bi-allelic ASCC1 mutations cause spinal muscular atrophy with congenital bone fractures 2 (SMABF2), characterized by severe prenatal-onset muscle weakness, neonatal hypotonia, arthrogryposis, and congenital bone fractures 4. Loss of ASCC1 function impairs osteoblast differentiation while promoting adipogenesis through downregulation of RUNX2 and SERPINF1 and inhibition of TGF-β/SMAD signaling 5. ASCC1 polymorphisms are associated with osteoporosis and obesity risk in postmenopausal women 6. ASCC1 RNA overexpression correlates with poor survival in certain cancers and genetic instability 1.