FOSB encodes a member of the AP-1 transcription factor family that acts as a DNA-binding transcription factor regulating gene expression through RNA polymerase II. The protein exhibits lower transactivation activity than its isoform 1 and may function as a transcriptional inhibitor when bound to JUN. FOSB shows increased stability compared to isoform 1, with a half-life of approximately 9.5 hours in cell culture. FOSB plays context-dependent roles in multiple disease states. In non-small cell lung cancer, FOSB expression exhibits contrasting prognostic effects depending on TP53 status: it predicts favorable outcomes in wild-type TP53 tumors but poor outcomes in TP53-mutant cancers 1. FOSB involvement extends to benign and malignant soft tissue tumors, where gene rearrangements occur in epithelioid hemangioma, pseudomyogenic hemangioendothelioma, and osteoid osteoma 2. Recent analysis identifies FOS/FOSB fusion-positive meningiomas as a distinct molecular subgroup with benign behavior and unique AP-1 activation patterns 3. In liver cancer, FOSB expression correlates with survival outcomes 4. FOSB also participates in cutaneous squamous cell carcinoma progression through the Wnt/β-catenin signaling pathway 5 and keloid fibroproliferation via the Piezo1/YAP axis 6. Additionally, FOSB expression in the nucleus accumbens is implicated in reward-dependent learning and addiction-related neuroplasticity.