IGF-II R (insulin-like growth factor 2 receptor), also known as IGF2R or M6P/IGF2R, is a multifunctional type I transmembrane glycoprotein. Its primary function is to act as a "scavenger receptor," binding and internalizing ligands such as insulin-like growth factor-II (IGF-II) and lysosomal enzymes marked with mannose-6-phosphate, thereby mediating their lysosomal degradation and negatively regulating cell growth, proliferation, and metabolism. This receptor plays a crucial role in embryonic development, tumor suppression, and metabolic homeostasis. Unlike IGF1R, its cytoplasmic tail is short and lacks tyrosine kinase activity. It primarily inhibits pro-growth signals by clearing circulating IGF-II through an endocytosis-degradation pathway, functioning as a tumor-suppressive "scavenger." As a classic tumor suppressor, its gene deletion or functional inactivation is commonly observed in various cancers, leading to abnormal activation of pro-growth signaling pathways.