WLS (Wnt ligand secretion mediator) is a transmembrane protein that serves as an essential chaperone for the secretion of all Wnt signaling proteins 1. The protein regulates Wnt protein sorting and secretion through a feedback regulatory mechanism, controlling expression, subcellular localization, binding, and organelle-specific association of Wnt proteins 1. Structurally, WLS belongs to the GOLD domain seven-transmembrane helix (GOST) protein family and functions as a membrane trafficking and secretion chaperone for lipidated Wnt proteins 2. During Wnt biogenesis, WLS binds to enzymatically lipidated Wnt proteins and facilitates their transport from the endoplasmic reticulum to the extracellular space, with calreticulin serving as a chaperone to facilitate Wnt transfer from Porcupine to WLS 3. Biallelic pathogenic variants in WLS cause Zaki syndrome, a pleiotropic multiorgan condition characterized by microcephaly, facial dysmorphism, alopecia, syndactyly, renal agenesis, and heart defects 14. These mutations affect WLS protein stability and impair Wnt signaling, demonstrating the critical role of WLS in embryonic development 1. Mouse models suggest this condition may be potentially treatable with pharmacologic Wnt agonists 1.