ID2 is a transcriptional regulator that functions as a dominant-negative inhibitor of basic helix-loop-helix (bHLH) transcription factors by forming heterodimers that prevent their DNA binding and transcriptional activity. ID2 regulates diverse cellular processes including proliferation, differentiation, and apoptosis across multiple cell types and tissues. Mechanistically, ID2 operates through several key pathways: (1) It suppresses cell proliferation through Wnt signaling crosstalk, where retinoic acid downregulates ID2 expression via histone modifications at the Wnt-response element in the ID2 promoter, reducing keratinocyte proliferation 1. (2) ID2 influences immune cell differentiation, particularly promoting CD8+ T cell function in an IL-12-dependent manner when activated by butyrate, enhancing antitumor responses 2. (3) ID2 participates in the CDK6 regulatory axis affecting Th17 cell differentiation through histone deacetylase signaling 3. (4) ID2 regulates ferroptosis in oligodendrocyte progenitor cells through the transferrin pathway, affecting neuronal recovery in spinal cord injury 4. (5) ID2 modulates mesenchymal stem cell immunoregulatory capacity and microbiota composition relevant to colitis treatment 5. (6) ID2-ETS2 interactions regulate pro-tumoral microglia phenotypes in glioblastoma 6. ID2 expression is dynamically regulated during lymphocyte activation, with high baseline expression in resting T cells that decreases upon proliferation, while ID3 expression reciprocally increases 7. These findings establish ID2 as a critical mediator in immune regulation, cell fate decisions, and disease pathogenesis across cancer, autoimmunity, and neuroinflammation.