LDLRrelated

LDLRrelated refers to the LDL receptor-related protein (LRP) family, a group of single-pass transmembrane receptors that are structurally related to the LDL receptor. LRPs function primarily as endocytic receptors that bind a wide range of ligands and mediate their internalization and trafficking, supporting roles in lipid metabolism, clearance of extracellular complexes, and regulation of signaling pathways. In addition to endocytosis, several LRPs act as co-receptors in developmental signaling, including Wnt signaling.

Major members of the family include LRP1, LRP2 (megalin), LRP4, LRP5, and LRP6, as well as related receptors involved in tissue-specific processes. Although the classical LDL receptor binds apolipoprotein B-100 and ApoE-containing particles to clear cholesterol-rich lipoproteins, LRPs extend ligand binding to a broader repertoire, enabling tissue-specific uptake of proteins, vitamins, proteases, and hormones. Structural features shared across LRPs typically include an extracellular ligand-binding region rich in LDL receptor class A repeats, followed by epidermal growth factor-like repeats and β-propeller domains, a single transmembrane segment, and a cytoplasmic tail with internalization motifs that recruit clathrin-adaptor machinery.

Physiological roles are diverse: mediation of lipid transport, modulation of proteolysis and extracellular matrix turnover, and influence on signaling pathways such as Wnt. In the brain, LRP1 contributes to amyloid-beta clearance; in the kidney, megalin facilitates reabsorption; in development, LRP5/6 are essential co-receptors in Wnt signaling.

Clinical relevance includes associations with atherosclerosis risk, neurodegenerative diseases, and congenital disorders stemming from altered LRP function, highlighting their broad importance in lipid handling and cellular signaling.