PACSIN1 is a neuronal scaffolding protein with critical roles in synaptic function and cytoskeletal organization. Mechanistically, PACSIN1 coordinates synaptic vesicle endocytosis and recycling through its F-BAR and SH3 domains, enabling sustained neurotransmission 1. It regulates microtubule stability via MAPT interaction and actin dynamics through COBL and WASL binding, supporting neurite morphogenesis and axonal plasticity 2. Beyond neurons, PACSIN1 functions as an axon-derived ligand for Schwann cell survival receptor LRP1, promoting peripheral nerve repair through c-Jun and TrkC signaling 3. Disease relevance is substantial. De novo PACSIN1 mutations impair TRAF4 binding, unleashing TLR-7-mediated type I interferon production in systemic lupus erythematosus 4. PACSIN1 genetic variants associate with late-onset Parkinson's disease risk through endocytic recycling pathways 5. In Angelman syndrome, loss of UBE3A-mediated PACSIN1 degradation increases protein levels, impairing AMPA receptor recycling and synaptic plasticity 6. PACSIN1 overexpression in gastric cancer suppresses MHC-I antigen presentation and CD8+ T-cell infiltration, promoting immunoevasion 7. These findings establish PACSIN1 as a pleiotropic regulator of neuronal and innate immune function with therapeutic implications across multiple disease contexts.