Taken together, our results unveiled new conceptual and functional avenues in GBM with potential clinical implications, by demonstrating that sst5TMD4 is overexpressed in GBM and associated with GBM survival/progression and key pathophysiological processes in GBM biology (i.e., proliferation and migration capacity), likely by modulating different oncogenic signaling pathways (AKT/JAK-STAT/NF-κB/TGF-β). Here, NFKB1 is linked to glioblastoma.