The Functions and Possible Significance of Kremen as the Gatekeeper of Wnt Signaling in Development and Pathology

Kremen (Krm) was identified as a transmembrane protein that acts as a high-affinity receptor for Dickkopf (Dkk), inhibiting Wnt/β-catenin signalling by forming a complex with Dkk and Lrp5/6. This inhibition is crucial for proper embryonic development, particularly in anterior-posterior patterning in Xenopus embryos. Krm expression increases during mammalian development and is strong in mature tissues but reduced in tumor cells, suggesting its role in preventing tumorigenic transformation by regulating Wnt/β-catenin signalling. Krm's regulation of this pathway is vital for cell-fate determination, tissue patterning, and stem cell regulation, highlighting its significance as a gatekeeper in these processes.