The
urokinase plasminogen activator receptor-associated
protein (uPARAP/
Endo180) is already known to be a key
collagen receptor involved in
collagen internalization and degradation in mesenchymal cells and some macrophages. It is one of the four members of the
mannose receptor family along with a macrophage
mannose receptor (MMR), a
phospholipase lipase receptor (PLA2R), and a dendritic receptor (DEC-205). As a
clathrin-dependent endocytic receptor for
collagen or large
collagen fragments as well as through its association with
urokinase (uPA) and its
receptor (uPAR), uPARAP/
Endo180 takes part in extracellular matrix (ECM) remodeling, cell chemotaxis and migration under physiological (tissue homeostasis and repair) and pathological (
fibrosis,
cancer) conditions. Recent advances that have shown an expanded contribution of this multifunctional
protein across a broader range of biological processes, including vascular biology and innate immunity, are summarized in this paper. It has previously been demonstrated that uPARAP/
Endo180 assists in lymphangiogenesis through its capacity to regulate the heterodimerization of
vascular endothelial growth factor receptors (VEGFR-2 and VEGFR-3). Moreover, recent findings have demonstrated that it is also involved in the clearance of
collectins and the regulation of the immune system, something which is currently being studied as a
biomarker and a therapeutic target in a number of
cancers.