ATF1 is a cAMP-responsive transcription factor that binds cAMP response elements (CRE) in gene promoters and mediates PKA-induced transcriptional activation 1. It functions as part of transcription factor complexes with ATF4 and CREB1, participating in cAMP/PKA signal transduction pathways 2. In normal physiology, ATF1 regulates anti-inflammatory microglial responses in neuroinflammatory conditions, where it serves as a key regulator of anti-inflammatory disease-associated microglia phenotypes 2. ATF1 also promotes colorectal cancer progression through direct transcriptional regulation of PRRC2A, which activates oncogenic WNT and YAP signaling 3. Clinically, ATF1 is predominantly recognized through its involvement in sarcomas and mesotheliomas. ATF1 undergoes recurrent fusion with EWSR1/FUS genes in soft-tissue neoplasms, including clear cell sarcomas, angiomatoid fibrous histiocytomas, and mesothelial tumors, generating chimeric transcription factors that drive malignant transformation 45678. EWSR1-ATF1 fusion tumors occur predominantly in young patients and show aggressive biological behavior with propensity for local recurrence and poor prognosis 46. ATF1 rearrangements represent important diagnostic and prognostic markers in mesothelial lesions, distinguishing them from conventional mesotheliomas 7. Recognition of ATF1-fusion status is essential for accurate diagnosis and risk stratification in young patients with mesenchymal malignancies.