Villar-Quiles RN, Catervi F, Cabet E, et al. - In the present study, the researchers defined activating signal cointegrator 1 (ASC-1) neuromuscular function and the phenotypical spectrum correlated with thyroid hormone receptor interactor 4 (TRIP4) mutations. In 5 families with 7 novel TRIP4 mutations, clinical, molecular, histological, and MRI studies were done. The findings extend the TRIP4-associated phenotypic and molecular spectrum to include mild adult types with or without cardiomyopathy, link ASC-1 depletion with independent primary muscle involvement, and identify TRIP4 as a causative gene for several congenital muscle diseases, including nemaline, core centronuclear, and cytoplasmic-body myopathies. In addition, they identify ASC-1 as a novel cell cycle regulator with a key role in cell proliferation, and as a novel pathophysiological mechanism underline transcriptional coregulation defects.