LRP2/Megalin Protein, Human (282a.a, HEK293, His-StrepII)

LRP2/Megalin is a multiligand endocytic receptor (By similarity). It acts together with CUBN to mediate endocytosis of high-density lipoproteins (By similarity) and facilitates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides, and polymyxin B (By similarity). In the kidney, it mediates tubular uptake and clearance of leptin (By similarity) and enables leptin transport across the blood-brain barrier via endocytosis at the choroid plexus epithelium (By similarity). Neuronal endocytosis of leptin is essential for hypothalamic leptin signaling and regulation of feeding and body weight (By similarity). Additionally, it mediates endocytosis and lysosomal degradation of CST3 in kidney proximal tubule cells (By similarity) and facilitates renal uptake of 25-hydroxyvitamin D3 in complex with GC/DBP (By similarity). It also participates in renal uptake of metallothionein-bound heavy metals (PubMed:15126248) and, alongside CUBN, mediates reabsorption of myoglobin (By similarity). LRP2/Megalin contributes to kidney selenium homeostasis by endocytosing selenoprotein SEPP1 (By similarity) and supports renal uptake of the antiapoptotic protein BIRC5/survivin (PubMed:23825075). Furthermore, it mediates renal uptake of MMP2 in complex with TIMP1 (By similarity). During development, it endocytoses Sonic hedgehog protein N-product (ShhN) and facilitates its transcytosis (By similarity). In the embryonic neuroepithelium, it regulates BMP4 endocytic degradation, ensuring proper SHH localization in the ventral neural tube and patterning of the ventral telencephalon (By similarity). In the adult brain, it negatively modulates BMP signaling in the subependymal zone to promote neurogenesis (By similarity) and mediates albumin (ALB) endocytosis in astrocytes, enabling oleic acid synthesis (By similarity). It also influences optic nerve development by supporting SHH-dependent oligodendrocyte precursor cell migration and proliferation (By similarity). In reproductive tissues, it mediates uptake of SHBG-bound androgens and estrogens (By similarity). Additionally, it endocytoses angiotensin-2 and angiotensin 1-7 (By similarity) and promotes lysosomal degradation of CLU/APOJ-bound beta-amyloid protein 40 (By similarity). LRP2/Megalin is crucial for embryonic heart development and normal hearing, potentially through interactions with estrogen in the inner ear (By similarity).