UNC5C encodes a transmembrane netrin receptor that plays crucial roles in axon guidance and apoptosis regulation. As a netrin-1 receptor, UNC5C mediates axon repulsion by binding to netrin-1, which causes dissociation from polymerized tubulin (TUBB3) in microtubules, leading to increased microtubule dynamics and subsequent axon repulsion 1. The protein is involved in dorsal root ganglion axon projection toward the spinal cord and functions as part of guidance receptor complexes, including interactions with GPC3 that regulate cell migration in neural development 2. UNC5C also acts as a dependence receptor, inducing apoptosis when not bound to netrin ligands. In cancer, UNC5C frequently functions as a tumor suppressor that is silenced through promoter hypermethylation. Loss of UNC5C expression occurs in 94.3% of renal cell carcinomas 3, 78% of colorectal cancers 4, and 25% of gastric cancers 5. Restoration of UNC5C expression suppresses colony formation, inhibits tumor cell proliferation and migration, and enhances chemosensitivity 3. The gene shows evidence of positive evolutionary selection and has been associated with polycystic ovary syndrome subtypes 67. Located on chromosome 4-q23, UNC5C represents an important therapeutic target in multiple cancer types 8.