Igfbp2, or Insulin-like growth factor binding protein 2, was initially identified as an IGF system regulator. It controls the distribution, function, and activity of IGFs in the pericellular space. It is a developmentally regulated gene, highly expressed in embryonic and fetal tissues with expression decreasing after birth. It is involved in multiple signaling pathways and is of great biological importance in processes like development and disease [4].

In lung fibrosis, loss of Igfbp2 mediates alveolar type 2 cell senescence and promotes fibrosis. Intranasal delivery of recombinant Igfbp2 protects aged mice from weight loss and shows antifibrotic effects after bleomycin lung injury [1].

In the liver, Igfbp2-CreER knockin strain was used to label midlobular hepatocytes. These Igfbp2-expressing cells contribute to liver homeostasis and regeneration, increasing in abundance during homeostasis and replenishing lost hepatocytes after injury [2].

In breast cancer, adipocytes secrete Igfbp2 which limits breast cancer invasion by binding and sequestering cancer-derived IGF-II [3].

In glioma, the cancer-associated fibroblast-related gene Igfbp2 promotes glioma progression by inducing M2 macrophage polarization [5].

In diabetic kidney disease, Igfbp2 deficiency attenuates urine protein, renal pathological injury, and glomeruli hypertrophy in DKD mice, and Igfbp2 facilitates podocyte apoptosis via integrin α5/FAK-mediated mitochondrial damage [6].

In conclusion, Igfbp2 plays crucial roles in various biological processes and diseases. Gene-knockout or conditional-knockout mouse models have revealed its significance in lung fibrosis, liver homeostasis and regeneration, breast cancer invasion, glioma progression, and diabetic kidney disease. Understanding Igfbp2 through these model-based studies can provide insights into disease mechanisms and potential therapeutic targets.