SEMA6C is a transmembrane semaphorin expressed in skeletal muscle and certain neural tissues during development 1. Originally characterized as an axon guidance molecule, SEMA6C induces growth cone collapse in dorsal root ganglion and hippocampal neurons in a dose-dependent manner 1, functioning as a repulsive guidance cue for neural development. Beyond its classical neuronal role, SEMA6C exhibits surprising tumor-suppressive functions in pancreatic cancer by inhibiting the AKT/GSK3/β-catenin/cyclin D1 proliferation pathway 2. Conversely, in other cancer contexts, SEMA6C promotes cell viability through an adhesion-independent mechanism involving c-Abl and FAK activation, leading to YAP nuclear localization and enhanced survival under nutrient deprivation 3. This apparent paradox suggests context-dependent signaling through its intracellular domain. Emerging evidence links SEMA6C to metabolic and degenerative diseases: genome-wide association studies identify SEMA6C as protective against nephrolithiasis 4 and identify it as a potential drug target for migraine 5. Additionally, SEMA6C appears dysregulated in glaucoma-associated trabecular meshwork pathology 6 and sarcopenia 7, suggesting roles in tissue remodeling and cellular homeostasis. These diverse functions underscore SEMA6C's broader significance beyond axon guidance in human disease.