The functions and possible significance of Kremen as the gatekeeper of Wnt signalling 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 anterior embryonic development, as demonstrated in Xenopus embryos. During mammalian development, Krm1 expression increases with differentiation, but is reduced in various human tumor cells, suggesting its role in preventing tumorigenic transformation by regulating Wnt/β‐catenin signalling. Krm's regulation of this pathway is essential for cell-fate determination, tissue patterning, and stem cell regulation, highlighting its significance as a gatekeeper in these processes.