LRP2 (LDL receptor-related protein 2, also known as megalin) functions as a multiligand endocytic receptor that forms homodimers and undergoes pH-dependent conformational changes for ligand binding at cell surfaces and ligand release in endosomes 1. The protein plays critical roles in renal physiology by mediating receptor-mediated uptake of diverse molecules including myoglobin, albumin, metallothionein-bound heavy metals, and various proteins in proximal tubule cells 23. LRP2-mediated endocytosis is essential for normal kidney function, as genetic deletion provides protection against rhabdomyolysis-induced acute kidney injury by preventing toxic myoglobin uptake 2. The receptor also regulates autophagic processes in proximal tubular cells, where lipid overload can lead to autophagic stagnation and lysosomal dysfunction 43. Beyond the kidney, LRP2 is expressed in liver mesothelial cells where it mediates clusterin-induced fiber endocytosis during liver fibrosis resolution 5. Disease associations include Donnai-Barrow syndrome and autosomal recessive Stickler syndrome, with mutations affecting homodimer assembly and receptor function 16. LRP2 represents a therapeutic target, as pharmacological inhibition with cilastatin can prevent kidney injury in rhabdomyolysis models 2.