OLFML3 (olfactomedin like 3) encodes a secreted scaffold protein with diverse roles in development, cancer progression, and placental function. In glioblastoma, OLFML3 serves as a critical downstream target of the circadian regulator CLOCK-BMAL1 complex, functioning as a novel chemokine that recruits immune-suppressive microglia into the tumor microenvironment 1. This recruitment mechanism involves transcriptional upregulation of OLFML3, which subsequently activates the HIF1α-LGMN-CD162 signaling axis to promote microglial infiltration and polarization toward immunosuppressive phenotypes 2. OLFML3 also contributes to tumor angiogenesis through HIF1α-mediated upregulation of periostin, which activates TBK1 signaling in endothelial cells 3. Beyond cancer, OLFML3 demonstrates protective functions in pregnancy-related disorders, where it suppresses trophoblast apoptosis via the PI3K/AKT pathway and may serve as a therapeutic target for preeclampsia 4. The protein is expressed in various tissues including ocular tissues 5 and appears in heparin-enriched plasma proteomes associated with Alzheimer's disease pathology 6. These findings establish OLFML3 as a multifunctional secreted factor with significant roles in immune regulation, vascular biology, and cellular survival across different disease contexts.