ACTR6 (actin-related protein 6) is a nuclear chr12 remodeling protein essential for nucleolar structure and function 1. As a component of the SRCAP chr12 remodeling complex, ACTR6 regulates ribosomal DNA (rDNA) transcription through H2A.Z deposition in a nutrient-dependent manner: under high glucose conditions, it maintains active rDNA transcription, while under glucose starvation, it represses rDNA transcription independently of H2A.Z 1. Beyond nucleolar function, ACTR6 plays critical roles in cancer biology. In hepatocellular carcinoma, ACTR6 upregulation promotes cancer cell stemness and migration by activating the Hedgehog signaling pathway, increasing expression of stemness markers (c-Myc, Oct4, Nanog, Sox2) 2. ACTR6 has been identified as a prognostic biomarker in multiple cancer types: it associates with poor survival in non-small cell lung cancer as part of a macrophage-related signature 3, serves as a risk gene in HER2+ breast cancer prognostic models 4, and correlates with tumor microenvironment and drug sensitivity in osteosarcoma 5. Additionally, uncommon ACTR6 variants associate with suicide attempt risk and are aberrantly expressed in brains of suicide decedents 6. These findings establish ACTR6 as a multifunctional regulator linking metabolic signaling, chr12 remodeling, and cancer stemness.