Prolow-density lipoprotein receptor-related protein 1

LRP1 (low-density lipoprotein receptor-related protein 1) is a large endocytic receptor involved in cellular lipid homeostasis, apoptotic cell clearance, and the processing of multiple ligands including chylomicron remnants, alpha-2-macroglobulin, and TAU/MAPT protein (UniProt: Q07954). The protein modulates APP metabolism, kinase signaling, neuronal calcium signaling, and neurotransmission, suggesting broad relevance to neuronal homeostasis.

LRP1 is expressed widely and serves as a receptor for multiple physiological and pathogenic ligands. UniProt documentation associates LRP1 mutations with keratosis pilaris atrophicans and developmental dysplasia of the hip, though these are rare genetic conditions (UniProt: Q07954).

In Alzheimer's disease, LRP1 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: +0.40; Chaparral AD proteomics). This upregulation, documented across human AD brain subcellular fractions via TMT proteomics, aligns with the protein's known roles in TAU clearance and APP metabolism, suggesting altered receptor activity may contribute to AD pathology.