Kremen protein 1 (KREMEN1)

Kremen protein 1 is a type I transmembrane receptor encoded by the KREMEN1 gene located on human chromosome 22. It contains extracellular kringle, WSC, and CUB domains but lacks conserved motifs in its intracellular region. As a high-affinity receptor for several members of the Dickkopf family (notably DKK1), it forms part of a membrane complex that regulates canonical Wnt/β-catenin signaling by cooperating with Dkk proteins to block signal transmission through LRP5/6 co-receptors. This action is crucial for proper embryonic development—especially anterior-posterior patterning—and adult tissue homeostasis by controlling cell proliferation and differentiation signals. In addition to its role in signal modulation, Kremen protein 1 can induce apoptosis when unbound by ligand—a property characteristic of dependence receptors. Its expression is widespread in mature tissues but often reduced in tumors; this reduction may contribute to increased susceptibility toward tumorigenic transformation due to unchecked Wnt pathway activity. Currently there are no approved drugs targeting this molecule directly; however, it remains an important research focus given its central regulatory position within the Wnt/Dkk/LRP axis implicated across developmental biology and oncology[3][4][5][6][7][8].

Other names

Kringle containing transmembrane protein 1Dickkopf receptorKringle-containing protein marking the eye and the noseECTD13KRM1

Drugs or biologics that would target this molecule would likely act by modulating its interaction with Dickkopf proteins to regulate Wnt/β-catenin signaling—either inhibiting or enhancing pathway activity depending on therapeutic context. The main mechanism is antagonism of canonical Wnt signaling through formation of a ternary complex with Dkk and LRP5/6 leading to internalization/removal from the cell surface.