FOSB is an AP-1 transcription factor subunit that functions as a DNA-binding transcription factor with diverse roles in cellular regulation and disease. As a component of the AP-1 complex, FOSB exhibits transcriptional activity though typically lower than its isoform FOS, and can act as a transcriptional inhibitor when heterodimers with JUN lack activity 1. FOSB demonstrates greater stability than FOS with a half-life of ~9.5 hours, allowing more sustained transcriptional effects. Mechanism: FOSB regulates transcription through sequence-specific DNA binding to AP-1 target genes. Its activity is context-dependent; notably, FOSB function is modulated by p53 status in lung cancer, where wild-type p53 supports tumor-suppressive functions while mutant p53 enables oncogenic programs 1. FOSB also participates in mechanotransduction pathways, serving as a downstream target of the Piezo1/YAP signaling axis in keloid pathogenesis 2. Disease Relevance: FOSB rearrangements characterize specific tumor entities including epithelioid hemangioma, pseudomyogenic hemangioendothelioma, and meningiomas 345. Elevated FOSB expression correlates with poor prognosis in liver cancer and promotes cancer stem cell traits in cutaneous squamous cell carcinoma via the Wnt/β-catenin pathway 67. In myocardial infarction, FOSB mediates pro-inflammatory macrophage phenotyping through AP-1 activation 8. Clinical Significance: FOSB represents a novel prognostic biomarker in NSCLC when combined with TP53 mutation status, and its immunohistochemical detection aids diagnosis of FOS/FOSB-rearranged tumors.