Megalin (LRP-2/GP330), a member of the LDL receptor family, is an endocytic receptor expressed mainly in polarised epithelial cells. Identified as the pathogenic autoantigen of Heymann nephritis in rats, its functions have been studied in greatest detail in adult mammalian kidney, but there is increasing recognition of its involvement in embryonic development. The megalin homologue LRP-1 is essential for growth and development in Caenorhabditis elegans and megalin plays a role in CNS development in zebrafish. There is now also evidence for a homologue in Drosophila. However, most research concerns mammalian embryogenesis; it is widely accepted to be important during forebrain development and the developing renal proximal tubule. Megalin is also expressed in lung, eye, intestine, uterus, oviduct, and male reproductive tract. It is found in yolk sacs and the outer cells of pre-implantation mouse embryos, where interactions with cubilin result in nutrient endocytosis, and it may be important during implantation. Models for megalin interaction(s) with Sonic Hedgehog (Shh) have been proposed. The importance of Shh signalling during embryogenesis is well established; how and when megalin interacts with Shh is becoming a pertinent question in developmental biology.