SEMA3F (semaphorin 3F) is an axon guidance molecule with critical roles in neural development and cancer biology. Primary Function: SEMA3F mediates chemorepulsion and axon guidance through binding to neuropilin (NRP1/NRP2) and plexin coreceptors 1, regulating cell motility, adhesion, and cytoskeletal dynamics. In neural development, SEMA3F is essential for cranial motor neuron organization 2 and inner ear development, where biallelic variants cause nonsyndromic hearing loss through impaired furin-mediated processing 3. Mechanism: SEMA3F inhibits cell attachment and spreading by promoting Rac1 relocalization and lamellipodia collapse 1, opposite to VEGF's effects. The SEMA3F-NRP1/NRP2 axis regulates epithelial-mesenchymal transition and extracellular matrix degradation 4. Disease Relevance: SEMA3F functions as a tumor suppressor across multiple cancers. Genomic loss correlates with increased metastasis in head and neck squamous carcinoma through enhanced lymphangiogenesis 5. In breast cancer, SEMA3F loss drives CDK4/6 inhibitor resistance 6, while SEMA3F re-expression enhances docetaxel chemosensitivity via Hippo pathway regulation 7. In esophageal adenocarcinoma, SEMA3F positivity predicts favorable survival and reduced lymph node metastasis risk 8. Clinical Significance: SEMA3F serves as a prognostic biomarker and potential therapeutic target for preventing cancer progression and metastasis.