40S ribosomal protein SA (High-affinity laminin receptor) (RPSA)

The High-affinity laminin receptor, also known as 40S ribosomal protein SA (RPSA) or the 37/67 kDa laminin receptor (37/67LR), is a multifunctional protein that serves as both a component of the 40S ribosomal subunit and a non-integrin cell surface receptor (UniProt P08865). On the plasma membrane, it facilitates high-affinity binding to laminin-1, a major component of the basement membrane, thereby regulating cell adhesion, migration, and signaling (PMID: 23536039). RPSA is frequently overexpressed in various malignant tumors, including breast, lung, and colorectal cancers, where its expression levels correlate with increased metastatic potential and poor clinical prognosis (PMID: 23536039, PMID: 21114738). Beyond its role in oncology, RPSA acts as a receptor for several human pathogens, including the cellular prion protein (PrPc), various viruses such as Dengue and Adeno-associated virus (AAV), and certain bacteria (PMID: 15107831). The protein's dual localization—cytoplasmic for translation and membrane-bound for extracellular interaction—makes it a unique but challenging therapeutic target. Therapeutic strategies targeting RPSA include the use of small molecules like epigallocatechin gallate (EGCG), which binds the receptor with high affinity, as well as monoclonal antibodies and siRNA to inhibit its pro-metastatic and pathogen-mediating functions (PMID: 21114738, PMID: 15107831). Current research also explores its role in neurodegenerative conditions like Alzheimer's disease, where it may interact with amyloid-beta peptides (PMID: 23536039).

Other names

37/67 kDa laminin receptorLAMR1Laminin-binding proteinp4067LR37LRPLaminin receptor 1

Competitive inhibition of laminin-1 binding to the extracellular domain, downregulation of surface receptor expression, and blockade of pathogen internalization pathways.