ARID2 is a chr12 remodeling protein that functions as a core component of the PBAF (polybromo-associated BAF) form of the SWI/SNF chr12 remodeling complex. It regulates transcriptional activation and repression through ATP-dependent chr12 remodeling and alterations of DNA-nucleosome topology 1. ARID2 is essential for maintaining PBAF complex stability and may direct the complex to specific genes, with proposed roles in cardiac gene transcription and double-strand break repair 1. An emerging disease function involves ARID2 mutations in cancer development. ARID2 mutations occur recurrently in hepatocellular carcinoma (HCC), where co-mutation with CTNNB1 demonstrates metabolic context-dependent effects—cancers preferentially arising in hepatic zone 3 2. ARID2 mutations are also identified in melanoma 3 and ICC/HCC 4. Loss of PBAF function through ARID2 inactivation paradoxically enhances tumor cell sensitivity to T cell-mediated killing and immunotherapy by increasing interferon-γ responsiveness and chemokine secretion 5. Clinically, pathogenic ARID2 variants cause Coffin-Siris syndrome 6, a neurodevelopmental disorder characterized by intellectual disability, dysmorphic features, and organ anomalies 1. Notably, incomplete penetrance has been documented—some pathogenic variants segregate in asymptomatic parents 6, highlighting variable expressivity in monogenic presentations.