Protein naked cuticle homolog 2 (NKD2)

Protein naked cuticle homolog 2 (NKD2) is a protein encoded by the NKD2 gene in humans and is part of the Naked cuticle family, primarily recognized as a negative regulator of the canonical Wnt signaling pathway through its interaction with Dishevelled family proteins (DVL1, DVL2, DVL3)[1][3]. Unlike its close homolog NKD1, NKD2 also binds transforming growth factor alpha (TGFα) and functions as a basolateral sorting adaptor, guiding TGFα-containing secretory vesicles to the basolateral membrane of polarized epithelial cells, a process dependent on N-terminal myristoylation[1][2][6]. The protein is predominantly intrinsically unstructured, with most functional domains—such as the Dishevelled-binding region, EF-hand-like motif, and vesicle recognition motif—located in the N-terminal half[2]. NKD2’s regulatory role in Wnt signaling connects it to processes controlling stem cell self-renewal and tumorigenesis, with increased interest regarding its altered expression in several cancers (such as osteosarcoma)[5]. No direct interacting drugs or approved therapeutic targeting currently exist, but the modulation of Wnt pathway activity by NKD2 underlies its importance as a potential biomarker and future therapeutic target[3].

Other names

Naked-2hNkd2Naked2naked cuticle-2Dvl-binding protein NKD2NKD inhibitor of Wnt signaling pathway 2WNT signaling pathway inhibitornaked cuticle homolog 2