SEMA3A (semaphorin 3A) is a secreted axon guidance cue that functions primarily as a chemorepellent molecule in neuronal development and tissue homeostasis. The protein binds to neuropilin-1/plexin-A1 receptor complexes to inhibit axonal growth cone motility and guide neuronal migration 1. In the nervous system, SEMA3A plays critical roles in olfactory system development and pubertal control, with mutations causing hypogonadotropic hypogonadism with or without anosmia 2. Beyond neurodevelopment, SEMA3A functions in tissue homeostasis through context-dependent mechanisms. In articular cartilage, SEMA3A maintains the aneural state and prevents chondrocyte hypertrophy via PI3K pathway activation, protecting against osteoarthritis progression 3. During bone remodeling under mechanical loads, sensory nerve-derived SEMA3A promotes osteogenic differentiation while facilitating nerve withdrawal through ROCK2 pathway regulation 1. In lymphatic development, SEMA3A mutations impair vessel maturation and dendritic cell recruitment 2. SEMA3A also regulates immune responses by promoting M2 macrophage polarization through the Sema3A/XIAP/PAX6 pathway, supporting tissue repair 4. Clinically, dysregulated SEMA3A expression associates with pathological conditions: high SEMA3A promotes aggressive basal-like pancreatic cancer phenotypes and macrophage infiltration 5, while reduced SEMA3A contributes to thin endometrium-associated infertility 6. These findings suggest SEMA3A modulation as a potential therapeutic target across diverse diseases.