{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVPS41 is an essential subunit of the HOPS complex that regulates key steps in endolysosomal trafficking. It mediates the fusion of specialized carriers—such as those delivering lysosome‐associated membrane proteins directly from the trans‐Golgi network—with late endosomes, functioning in conjunction with SNARE proteins like VAMP7. VPS41’s recruitment to the late endosomal and lysosomal membranes, facilitated for example by its interaction with the C-terminal region of RILP, enables the proper delivery and degradation of endocytic cargo. In addition, the assembly of VPS41 into the HOPS complex (through critical interactions such as its RING domain binding with that of VPS18) ensures the execution of these membrane fusion events, while dynamic competition with CORVET components modulates this process."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in membrane trafficking, VPS41 exhibits neuroprotective functions that have been highlighted in models of Parkinson’s disease and related neurodegenerative disorders. Upregulation of human VPS41 has been shown to prevent dopaminergic neuron loss and reduce the accumulation of toxic protein aggregates—including misfolded α‐synuclein and amyloid‐β—presumably by enhancing lysosomal clearance and autophagic flux. Conversely, mutations in VPS41 that disrupt HOPS assembly interfere with lysosomal delivery and perturb intracellular signaling (notably affecting the TFEB/TFE3 axis), leading to neurodevelopmental phenotypes marked by ataxia, dystonia, and cerebellar abnormalities."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maaike S Pols, Eline van Meel, Viola Oorschot, et al. 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