Megalin, a multi-ligand endocytic receptor, and its participation in renal function and diseases: A review

The endocytosis mechanism is a complicated system that is essential for cell signaling and survival. Megalin, a membrane-associated endocytic receptor, and its related proteins such as cubilin, the neonatal Fc receptor for IgG, and NaPi-IIa are important in receptors-mediated endocytosis. Physiologically, megalin uptakes plasma vitamins and proteins from primary urine, preventing their loss. It also facilitates tubular retrieval of solutes and endogenous components that may be involved in modulation and recovery from kidney injuries. Moreover, megalin is responsible for endocytosis of xenobiotics and drugs in renal tubules, increasing their half-life and/or their toxicity. Fluctuations in megalin expression and/or functionality due to changes in its regulatory mechanisms are associated with some sort of kidney injury. Also, it's an important component of several pathological conditions, including diabetic nephropathy and Dent disease. Thus, exploring the fundamental role of megalin in the kidney might help in the protection and/or treatment of multiple kidney-related diseases. Hence, this review aimed to explore the physiological roles of megalin in the kidney and their implications for kidney-related injuries.