Epithelia lining the proximal convoluted epithelium and the visceral yolk sac in rodents are characterized by their ability to internalize and degrade many proteins facing their apical pole. It has become apparent over the last decade that this property is mediated through a very high endocytic activity and the expression of at least two distinct multiligand receptors, cubilin and megalin, characterized by the accumulation of ligand-binding units, LDL receptor class A repeats and CUB domains, respectively. We review here evidence that both receptors are involved in proximal tubule function and embryonic development.