ROR2 is a receptor tyrosine kinase-like orphan receptor that functions as a key regulator of cellular plasticity and developmental processes. Mechanistically, ROR2 acts as a non-canonical Wnt signaling receptor, particularly for WNT5A ligand, activating ROR2 homooligomerization to initiate downstream signaling cascades 1. ROR2 operates within diverse signaling pathways including Wnt/Ca2+ signaling 2 and can mediate phosphorylation events like PlexinB1 activation in vascular contexts 3. Developmentally, ROR2 is essential for proper skeletal development; mutations cause Robinow syndrome (autosomal recessive) and brachydactyly B1, characterized by mesomelic shortening and skeletal abnormalities 4. ROR2 expression is primarily embryonic but is aberrantly reactivated in cancers. In disease contexts, ROR2 drives aggressive phenotypes across multiple cancer types. In pancreatic ductal adenocarcinoma, ROR2 promotes epithelial-to-mesenchymal transition, confers resistance to KRAS inhibitors, and marks metaplasia-like identities 5. In breast cancer, ROR2 enhances stem-like cell properties and tumor-initiation capacity 1. ROR2 is also implicated in age-related macular degeneration pathology through pericyte activation 3. These oncogenic roles have prompted development of therapeutic ROR2-targeting approaches, including conditionally active antibody-drug conjugates showing efficacy across multiple cancer xenograft models 6.