PTK7 is a catalytically inactive receptor tyrosine kinase that functions as a signaling node in Wnt pathway regulation and cell-cell communication 1. Despite lacking kinase activity, PTK7 operates through heterodimerization with active receptors and serves as a positive allosteric modulator of GPR133 signaling in glioblastoma 2. The protein coordinates diverse cellular processes including cell adhesion, migration, and cytoskeleton reorganization, contributing to embryogenesis and angiogenesis. Clinically, PTK7 is significantly overexpressed on tumor-initiating cells across triple-negative breast cancer, ovarian cancer, and non-small cell lung cancer 1. This enrichment links PTK7 to metastasis, poor prognosis, and treatment resistance 3. Multiple therapeutic strategies have emerged: PTK7-targeted antibody-drug conjugates (ADCs) using microtubule inhibitors or topoisomerase I inhibitors demonstrate sustained tumor regressions and outperform standard chemotherapy 4. Emerging approaches include aptamer-based degraders and CAR-T therapies targeting PTK7-positive tumors 3. A first-in-human clinical trial of cofetuzumab pelidotin (PF-06647020), a PTK7-targeted ADC, showed objective response rates of 19-27% in heavily pretreated ovarian, lung, and breast cancer patients, with PTK7 tumor expression predicting responder status 5. These findings establish PTK7 as an actionable cancer target despite its catalytic inactivity.