ID4 (Inhibitor of DNA Binding 4) 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 1. Unlike other ID family members (ID1-3) that promote oncogenesis, ID4 displays distinct, context-dependent functions across development and disease 1. During development, ID4 regulates neurogenesis, lymphoid organogenesis, mammary gland development, and spermatogenesis 2, while promoting stem cell survival and differentiation timing 1. In mammary epithelium, ID4 controls luminal lineage commitment and developmental pathways 3. Mechanistically, ID4 expression is regulated through an NAD+-SIRT2-H3K18Ac axis, where SIRT2-mediated histone acetylation at H3K18 influences ID4 levels 4. ID4 is epigenetically silenced in advanced cancers including prostate cancer through EZH2-dependent H3K27me3 marking and promoter methylation 5, yet paradoxically overexpressed in some basal-like breast cancers where it may suppress BRCA1 function and confer poor prognosis 3. ID4 gene polymorphisms may influence bone metabolism in menopausal women 6. These findings position ID4 as a lineage-dependent regulator with both tumor-suppressive and proto-oncogenic roles depending on cellular context.