Wnt5a

Wnt5a is a secreted signaling protein of the WNT family. In humans, it is encoded by the WNT5A gene and functions as a key mediator of non-canonical Wnt signaling.

Wnt5a primarily activates non-canonical pathways, such as the planar cell polarity and Wnt/Ca2+ cascades, influencing cell movement, polarity, and tissue morphogenesis during embryonic development. It can interact with Frizzled receptors, often in conjunction with co-receptors such as ROR2 or RYK, to transmit signals that do not stabilize beta-catenin. Wnt5a is typically secreted after lipid modification by the porcupine (PORCN) enzyme, which is required for its activity.

Expression patterns are broad in embryonic tissues and persist in various adult tissues, where Wnt5a regulates processes including limb development, neural tube closure, cardiovascular morphogenesis, and neural crest migration.

Clinical relevance: Mutations in WNT5A cause Robinow syndrome, a developmental disorder affecting skeletal elements. In cancer biology, Wnt5a has context-dependent roles, sometimes inhibiting canonical Wnt signaling and suppressing tumor growth, while in other settings it promotes invasion and metastasis via non-canonical pathways. The duality reflects tissue context, receptor expression, and downstream signaling components.