biostudies-literatureUnknown11(41)Pareek GStress granules (SGs) are dynamic RNA-protein assemblies that form in response to cellular stress and must be efficiently disassembled to restore normal cell function. Valosin-containing protein (VCP), an enzyme implicated in neurodegenerative diseases, is essential for SG disassembly, but whether and how this process is coordinated with SG assembly remains unclear. Here, we identify the VCP cofactor, Alveolar soft part sarcoma locus (ASPL) as a key regulator linking SG assembly and disassembly. ASPL promotes SG assembly by facilitating biomolecular condensation of Ras guanosine triphosphatase-activating protein-binding protein (G3BP) and stabilizing its interactions with other SG proteins. ASPL also facilitates phosphorylation and activation of VCP by UNC-51-like kinases 1 and 2 (ULK1/2),Science advanceseady3735https://www.ebi.ac.uk/biostudies/studies/S-EPMC12506973biostudies-literatureASPL couples the assembly of stress granules with their VCP-mediated disassembly.PMC12506973Wu JWang BDharmat RQuan HMaxwell BLi-Harms XPruett-Miller SMBanerjee PNourse ABasalla JLLi DMessing JKim HJMahendran TSWang YDSingh ACarisey AFPounds SPareek GNi YKundu MLu JTaylor JPRana MSKalathur RFreibaum BDfalseASPL couples the assembly of stress granules with their VCP-mediated disassembly.Stress granules (SGs) are dynamic RNA-protein assemblies that form in response to cellular stress and must be efficiently disassembled to restore normal cell function. Valosin-containing protein (VCP), an enzyme implicated in neurodegenerative diseases, is essential for SG disassembly, but whether and how this process is coordinated with SG assembly remains unclear. Here, we identify the VCP cofactor, Alveolar soft part sarcoma locus (ASPL) as a key regulator linking SG assembly and disassembly. ASPL promotes SG assembly by facilitating biomolecular condensation of Ras guanosine triphosphatase-activating protein-binding protein (G3BP) and stabilizing its interactions with other SG proteins. ASPL also facilitates phosphorylation and activation of VCP by UNC-51-like kinases 1 and 2 (ULK1/2),2025-01-01T00:00:00Z2025 Oct2026-06-04T09:10:16.913Z2026-05-07T03:12:03.718ZS-EPMC125069734106105210.1126/sciadv.ady3735