Mouse oocytes store protein aggregates in specialized compartments called endolysosomal vesicular assemblies (ELVAs), which are composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. These compartments sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation to promote healthy embryogenesis. Failure to degrade these aggregates in ELVAs leads to early embryonic arrest. ELVAs relocate to the cortex during oocyte maturation in an actin-dependent manner and disappear in the 2-cell embryo, coinciding with increased lysosomal exocytosis. The degradative activity in ELVAs increases during oocyte maturation, and the removal of ELVAs triggers lysosomal activation and premature lysosomal exocytosis. ELVAs degrade specific sequestered proteins, including disease-linked TDP-43 and KIT, upon oocyte maturation. Preventing lysosomal degradation during oocyte maturation causes aggregate accumulation in ELVAs and forms defective eggs, while injecting zygotes with mRNAs encoding for aggregating proteins disrupts early embryonic development and causes rapid embryonic death. This study reveals a novel strategy for oocytes to maintain cytoplasmic homeostasis by sequestering and degrading protein aggregates during their long life.Mouse oocytes store protein aggregates in specialized compartments called endolysosomal vesicular assemblies (ELVAs), which are composed of endolysosomes, autophagosomes, and proteasomes held together by a protein matrix formed by RUFY1. These compartments sequester aggregated proteins, including TDP-43, and degrade them upon oocyte maturation to promote healthy embryogenesis. Failure to degrade these aggregates in ELVAs leads to early embryonic arrest. ELVAs relocate to the cortex during oocyte maturation in an actin-dependent manner and disappear in the 2-cell embryo, coinciding with increased lysosomal exocytosis. The degradative activity in ELVAs increases during oocyte maturation, and the removal of ELVAs triggers lysosomal activation and premature lysosomal exocytosis. ELVAs degrade specific sequestered proteins, including disease-linked TDP-43 and KIT, upon oocyte maturation. Preventing lysosomal degradation during oocyte maturation causes aggregate accumulation in ELVAs and forms defective eggs, while injecting zygotes with mRNAs encoding for aggregating proteins disrupts early embryonic development and causes rapid embryonic death. This study reveals a novel strategy for oocytes to maintain cytoplasmic homeostasis by sequestering and degrading protein aggregates during their long life.