ID1 (inhibitor of DNA binding 1) is a transcriptional regulator that functions as a negative regulator of basic helix-loop-helix (bHLH) transcription factors through heterodimer formation, controlling diverse cellular processes including differentiation, stemness, and immune regulation. Mechanistically, ID1 operates through multiple pathways depending on cellular context. In tumor-associated macrophages, ID1 interacts with STAT1 to promote its cytoplasmic redistribution, inhibiting transcription of SerpinB2 and CCL4, thereby maintaining cancer stem cell niches and suppressing CD8+ T cell infiltration 1. In keratinocytes, ID1 functions downstream of the AhR-Ovol1 axis to promote epidermal barrier maintenance and immune homeostasis 2. In the acute myeloid leukemia microenvironment, ID1 interacts with the E3 ubiquitin ligase RNF4 to stabilize SP1, which transactivates ANGPTL7 to support leukemia stem cells 3. In ovarian cancer stem cells, autophagy-mediated ID1 degradation releases TCF12 to activate SLC31A1, promoting cisplatin sensitivity 4. ID1 expression is dysregulated across multiple malignancies. High ID1 expression correlates with poor outcomes in colorectal cancer 1, pancreatic ductal adenocarcinoma 5, and diffuse intrinsic pontine glioma, where H3.3K27M oncohistones directly enhance CREB5-mediated ID1 expression 6. TGFβ signaling dynamically regulates ID1 through Nur77-mediated mechanisms controlling colon cancer stemness and therapy resistance 7. Clinically, targeting ID1 represents a promising therapeutic strategy across multiple cancer types, particularly when combined with immunotherapy or conventional chemotherapy 1.