FAM131B is a chromosome 7-localized gene involved in oncogenic fusion events and replication stress regulation. In pediatric low-grade gliomas, FAM131B participates in constitutive MAPK pathway activation through formation of FAM131B-BRAF fusion proteins via 7q34 deletions 1. These fusion events remove BRAF's N-terminal inhibitory domains, generating a constitutively active kinase with transforming activity 1. FAM131B-BRAF fusions represent an alternative mechanism to the more common KIAA1549-BRAF fusion, occurring in approximately 0.6% of pediatric low-grade glioma cases 2 and appearing more frequently in adult pilocytic astrocytomas 3. Beyond fusion-driven oncogenesis, the FAM131B-AS2 long noncoding RNA (located at 7q34) promotes glioblastoma progression by stabilizing replication protein A1 through ubiquitin-specific peptidase 7 recruitment, thereby mitigating replication stress and protecting single-stranded DNA 4. FAM131B upregulation correlates with poor glioblastoma survival and suppresses anti-tumor immunity by inhibiting CD8+ T-cell infiltration 4. Additionally, FAM131B shows significant overexpression in ACTH-secreting corticotroph pituitary adenomas associated with Cushing's disease 5. SNP array analysis and next-generation sequencing effectively detect FAM131B-BRAF fusions, supporting clinical diagnostic applications 6.