The insulin-like growth factor 2 receptor (IGF2R) is a transmembrane glycoprotein with a complex structural architecture critical for its multifaceted biological roles. Structurally, IGF2R comprises seven extracellular domains organized into repeating β-sheets and α-helical motifs, facilitating ligand binding and intermolecular interactions. These extracellular regions are linked to a short transmembrane domain and a cytoplasmic tail containing tyrosine phosphorylation motifs that mediate intracellular signaling. Unlike typical growth factor receptors, IGF2R lacks intrinsic tyrosine kinase activity but recruits adaptor proteins like Grb2 and Shc to propagate downstream signals. Functionally, IGF2R serves dual roles as a clearance receptor for IGF2 and a transport regulator for lysosomal enzymes via mannose-6-phosphate (M6P) recognition. This dual functionality enables precise regulation of IGF2 bioavailability and proper lysosomal enzyme trafficking, crucial for normal cellular homeostasis. Emerging evidence highlights its tumor-suppressive properties through IGF2 sequestration and modulation of autophagy pathways. Furthermore, structural studies reveal conformational flexibility in its extracellular domains, allowing allosteric regulation during ligand binding and receptor internalization. Dysregulation of IGF2R has been implicated in developmental abnormalities and cancer progression, making it a potential therapeutic target for diseases characterized by IGF2 overexpression.