VPS10P domain receptors are intracellular sorting receptors which direct their protein cargo to destined subcellular localizations. Although it seemed that functions of VPS10P receptors in the brain are restricted to neurons, it turned out they are also relevant for glial cells, including microglia, which dependently on pathological context may acquire different functional properties. For instance, during glioblastoma progression, microglia along with infiltrating macrophages are reprogrammed, so instead of fighting with glioma they support it, mainly through secretion of pro-tumorigenic factors. Such cells are collectively called glioma associated microglia and macrophages (GAMs) and constitute up to 30% of the tumor mass. We hypothesize that SorLA, a member of the VPS10P family, drives microglial release of glioma-supporting factors, while its lack favors secretion of pro-inflammatory agents. To explore it, using in vitro models we verified that microglial expression of SorLA is regulated by the activation mode of the cells and we identified SorLA protein targets which may influence the type of microglial response. Interestingly, we observed that SorLA binds TNFα via EGF/β-propeller domain and thereby restricts its release. Our in vivo experiments demonstrated that SorLA-deficient mice develop smaller gliomas than wild-type animals, which coincidences with increased inflammatory state of tumor microenvironment manifested by changes in microglia morphology, immune cells influx and increased levels of necroptosis markers. In summary, we propose that SorLA is a key player in shaping properties of GAMs and its depletion unlocks anti-tumor response.Studies were supported by the NCN, Poland (2020/37/B/NZ3/00761;2023/49/N/NZ4/01690), and the IDUB at the UW, Poland.