GPC5 (glypican 5) encodes a cell surface heparan sulfate proteoglycan that functions as a tumor suppressor and regulator of cellular processes. The protein is anchored to the plasma membrane via glycosylphosphatidylinositol and plays crucial roles in growth regulation and cellular signaling 1. GPC5 exhibits tumor suppressive functions in multiple cancer types, notably in lung cancer where it suppresses progression and metastasis through dual mechanisms: intracellularly by enhancing CTDSP1 expression via the AhR-ARNT pathway, and extracellularly through exosome-mediated delivery of miR-26b that targets PTK2 in lymphatic endothelial cells 2. In gastric cancer, GPC5 expression is stabilized by the long non-coding RNA GPC5-AS1, which acts as a molecular sponge for miR-93/106a, leading to suppressed cell proliferation 3. The gene demonstrates clinical significance beyond cancer, with genetic variants in its 5'-upstream region conferring lung cancer risk in never smokers 4, and involvement in ethanol response behaviors across multiple species 5. GPC5 is also implicated in neuronal vulnerability in Alzheimer's disease, where specific neuronal subtypes expressing GPC5 accumulate pTau but remain protected from degeneration 6.