KREMEN1 is a transmembrane receptor that primarily functions as a Wnt/β-catenin pathway regulator. As a receptor for Dickkopf proteins (DKK1/2), KREMEN1 cooperates to inhibit canonical Wnt signaling by promoting endocytosis of Wnt receptors LRP5 and LRP6 1. In the absence of DKK1 ligand binding, KREMEN1 maintains LRP5/6 at the cell membrane, potentiating Wnt signaling [UniProt]. KREMEN1 also triggers ligand-independent apoptosis, an activity inhibited upon DKK1 binding [UniProt]. During development, KREMEN1 regulates limb patterning by attenuating Wnt signaling and negatively regulates bone formation and hair cell fate specification in the developing cochlea [UniProt]. Neurologically, Kremen1+ striatonigral neurons suppress locomotion by inhibiting dopaminergic neurons through GABBR1-mediated signaling, opposing the locomotion-promoting effects of Calb1+ neurons 2. Beyond developmental functions, KREMEN1 serves as an alternative ACE2-independent receptor for SARS-CoV-2 entry 3, 4, and functions as a host entry receptor for coxsackievirus A10 and related enteroviruses, with VP2 residue N142 being critical for viral attachment 5, 6. Clinically, biallelic KREMEN1 variants cause ectodermal dysplasia with severe tooth agenesis and sparse hair 1, 7, and KREMEN1 variants show protective associations with primary open-angle glaucoma 8.