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SH3 domain containing GRB2 like 2, endophilin A1 (SH3GL2) is an adaptor protein notable for its role in synaptic vesicle endocytosis, receptor trafficking, and membrane remodeling through its BAR domain, which senses and induces membrane curvature[1][2][4][13]. SH3GL2 is abundant in neuronal tissues, particularly the brain, and is essential for maintaining synaptic homeostasis, modulating autophagy in response to neuronal activity and calcium influx, and regulating protein quality control at synapses[3][5]. Mutations in SH3GL2 are associated with neurodegenerative risk, particularly Parkinson’s disease, where they impair synaptic autophagy induction. SH3GL2 also functions as a tumor suppressor in certain cancers, regulating apoptotic pathways and intracellular signaling networks[1][5].
Mechanisms inferred from protein function: regulation of membrane curvature and trafficking, modulation of synaptic vesicle endocytosis, impact on autophagy via calcium-sensitive conformational changes[3][4][5] Not directly targeted by approved drugs, as of current literature
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