Kringle containing transmembrane protein 1 (KREMEN1)

Kringle containing transmembrane protein 1 (KREMEN1) is a single-pass transmembrane receptor primarily known for its high-affinity binding to Dickkopf proteins (DKK1/2), acting as a negative regulator of canonical Wnt/β-catenin signaling. Through interaction with DKK1 and the coreceptors LRP5/6, KREMEN1 mediates clathrin-dependent endocytosis of the Wnt receptor complex, blocking Wnt signaling and influencing cell fate decisions in various tissues such as the cochlea, skin, teeth, limbs, and hair follicles. KREMEN1 also has Wnt-independent roles, including potential induction of apoptosis and participation as a viral entry receptor for certain pathogens such as Coxsackievirus A10 and, possibly, SARS-CoV-2. Mutations in KREMEN1 can cause syndromic ectodermal dysplasias. The protein contains kringle, WSC, and CUB domains, and its developmental function is critical for proper differentiation and tissue patterning.

Other names

Kremen protein 1KRM1KREMENDickkopf receptorKringle domain-containing transmembrane protein 1ECTD13Kringle-containing protein marking the eye and the nose

Drugs or molecules that modulate KREMEN1 typically act by blocking or enhancing its inhibition of Wnt/β-catenin signaling, either by mimicking/inhibiting DKK1 interaction or modulating KREMEN1-LRP5/6 complex formation