Protein wntless homolog (WLS)

Protein wntless homolog (WLS) is an integral membrane protein responsible for mediating the secretion and sorting of Wnt ligands, a family of secreted, lipid-modified signaling proteins essential for cell communication, embryonic development, and tissue homeostasis[1][3][4][5]. WLS binds Wnt proteins within the endoplasmic reticulum and facilitates their trafficking through the secretory pathway to the cell surface, enabling Wnt ligands to reach and activate their target receptors on neighboring cells[1][2][3][4]. WLS is evolutionarily conserved and indispensable for canonical and non-canonical Wnt signaling, with loss-of-function mutations implicated in developmental disorders, including Zaki syndrome[2][3][5]. While not a classical receptor, enzyme, or transporter, WLS is a critical node in the Wnt signaling pathway, making it a potential target for modulating Wnt-driven diseases—though no approved drugs directly target WLS at present.

Other names

WntlessC1orf139GPR177UNQ85/PRO18667EVIFLJ23091MRPmig-14Integral membrane protein GPR177Protein evenness interrupted homologZKS

Drugs (if developed) would likely inhibit or modulate WLS to disrupt Wnt ligand secretion, thereby modulating Wnt pathway signaling implicated in development and disease