C15orf39 (PRMT2IP) is a multifunctional protein with distinct roles in inflammation and cancer. Primarily, C15orf39 negatively regulates microglial inflammatory responses 1. It inhibits NF-κB signaling by interacting with PRMT2, stabilizing IκBα and reducing pro-inflammatory cytokine production (IL-6 and TNFα) 12. This regulatory function protects against ischemic stroke; Mendelian randomization analysis demonstrates that downregulation of C15orf39 causally associates with elevated ischemic stroke risk 32. Conversely, C15orf39 overexpression alleviates ischemia-induced brain injury in mouse models 2. In contrast to its protective neuroinflammatory role, C15orf39 promotes gastric carcinogenesis through PI3K/AKT signaling 4. It acts downstream of PI3K/AKT/FOXK2 axis, enhancing GC cell proliferation, migration, drug resistance, and cell cycle progression 4. C15orf39 is a MAPK1 substrate 5, and its upregulation in gastric cancer tissues correlates with poor clinical outcomes 4. These findings reveal context-dependent functions: protective against neuroinflammation but oncogenic in gastric cancer, suggesting C15orf39 as both a therapeutic target and biomarker depending on disease context.