ARID3C (AT-rich interaction domain 3C) is a transcription factor located on chromosome 9 that plays a critical role in myeloid cell differentiation. Its primary function is to regulate monocyte-to-macrophage differentiation by activating genes essential for this process, including STAT3, STAT1, and JUNB 1. Mechanistically, ARID3C forms a nuclear-cytoplasmic shuttling complex with NPM1, which is required for its translocation to the nucleus where it binds DNA promoters 1. Mutation of the ARID3C-NPM1 binding interface prevents nuclear localization and ablates transcriptional activity 1. ARID3C belongs to the ARID3 subfamily, which is distinguished by the REKLES domain that mediates protein-protein interactions, multimerization, and subcellular localization 2. The protein exhibits selective expression in B lineage lymphocytes and undergoes lipid raft localization following B cell receptor stimulation 3. Regarding disease relevance, ARID3C expression is decreased in hepatocellular carcinoma and correlates with improved overall survival, suggesting a tumor-suppressive role [PMID:36034939; 45]. ARID3C was identified as a component of a signaling nexus involving Wnt pathway regulators in ovarian cancer 5. Clinically, ARID3C may serve as a prognostic biomarker; however, its therapeutic potential remains to be characterized.