Increasing evidence demonstrates the importance of Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling as a pivotal molecular hub active in critical microenvironmental cellular populations, such as glioma cells, reactive astrocytes, and stromal and immune cells, that drives not only aggressive growth, invasion, treatment resistance, and cancer cell stemness but also tumor-mediated immunosuppression. The gene discussed is SOAT1; the disease is glioma.