Protein naked cuticle homolog 1 (NKD1)

Protein naked cuticle homolog 1 (NKD1) is a member of the Naked cuticle (Nkd) family and functions as a cytoplasmic antagonist of the canonical Wnt signaling pathway[1][3][4]. NKD1 contains an EF-hand calcium-binding motif, is membrane-associated (via N-terminal myristoylation), and primarily inhibits Wnt/β-catenin signaling by binding Dishevelled (Dvl) family proteins, leading to their destabilization[1][3][5]. Loss or mutation of NKD1 disrupts this inhibition, resulting in β-catenin stabilization and increased cell proliferation[3]. Mutations in NKD1 have been identified in a subset of DNA mismatch repair-deficient colorectal cancers, implicating NKD1 in the negative regulation of the Wnt pathway during tumorigenesis[1][3]. As a feedback inhibitor, NKD1 ensures proper modulation of Wnt signal strength and duration; defects in its function are associated with increased cancer risk, especially when other classic Wnt regulators are not mutated[1][3]. Current evidence supports its biological and disease relevance, but there are no known direct therapeutic drugs targeting NKD1 itself.

Other names

Protein naked cuticle homolog 1NKD1NKDPP7246Naked-1hNkdhNkd1Naked1Dvl-binding proteinWNT signaling pathway inhibitornaked cuticle homolog 1naked cuticle-1naked-1