IGFBPL1 is an insulin-like growth factor binding protein-like protein that functions as a putative tumor suppressor and neuroprotective regulator. IGFBPL1 exerts its primary effects through IGF-1 receptor (IGF1R) signaling pathways 1. In the nervous system, IGFBPL1 acts as a master driver of microglial homeostasis, promoting resolution of neuroinflammation by resetting transcriptome signatures toward a homeostatic state 2. IGFBPL1 is secreted by astrocytes in response to α-synuclein oligomers via sustained NF-κB pathway activation, providing neuroprotection against neuroinflammation 3. Additionally, SVZ-derived neural precursor cells tune striatal connectivity through IGFBPL1 secretion, supporting cognitive functions 4. In peripheral tissues, IGFBPL1 inhibits macrophage lipid accumulation by enhancing IGF1R/LXRα/ABCG1 pathway activation, providing anti-atherosclerotic effects 5. IGFBPL1 also regulates retinal ganglion cell axon growth through IGF-1-mediated signaling and mTOR phosphorylation 1. Clinically, IGFBPL1 expression is frequently silenced in multiple cancers through epigenetic hypermethylation. In breast cancer, IGFBPL1 methylation correlates with worse overall survival and disease-free survival 6. In esophageal squamous cell carcinoma, IGFBPL1 silencing promotes cancer growth via PI3K-AKT pathway activation, and restoration of IGFBPL1 expression inhibits tumor progression 7. In liver cancer, low IGFBPL1 expression is associated with better immunotherapy response 8.