Frizzled-5 is an approximately 62 kDa 7-TM glycoprotein that is one of at least ten Frizzled family Wnt receptors (1, 2). Wnt engagement of Frizzled, with low density lipoprotein receptor-related proteins LRP-5 or LRP-6 acting as co‑receptors, stabilizes beta -catenin and promotes gene transcription that is important in development and tissue maintenance (1). Frizzleds can also signal through non-canonical pathways independently of LRPs (1). Mature mouse Frizzled-5 consists of a 212 amino acid (aa) extracellular domain (ECD), a 283 aa 7-TM region, and a 64 aa cytoplasmic domain with a PDZ binding motif (2, 3). The ECD includes a cysteine-rich region (CRD) that binds Wnts and is highly conserved among Frizzled proteins (1, 2, 4). Within the N-terminal ECD, human Frizzled-5 shares 95% aa sequence identity with mouse and rat Frizzled-5. Frizzled-5 is expressed in embryonic tissues (telencephalon, pituitary, thalamus, hypothalamus, eye, liver, spleen, lung, and kidney), in the adult retina, colon, and pancreatic islets, some cancer cell lines, human embryonic stem cells, and in some monocyte and lymphocyte populations (2-8). Frizzled-5 functions as a receptor for Wnt-5a, Wnt-9b, Wnt-10b, Wnt-2b, and Wnt-7a (3, 5, 9, 10). It plays a role in the maintenance of yolk sac and placental vasculature (ishikawa) and in the regression of vitreous vasculature during eye development (5, 6, 11). It mediates the synaptogenic effect of Wnt-7a, contributes to the development of neuronal polarity, and is required for neuronal survival in the thalamus (3, 12, 13). In macrophages and monocytes, Frizzled-5 signaling induces the production of inflammatory cytokines (7, 8).