ZAR1 (zygote arrest 1) is a maternal mRNA-binding protein essential for female fertility and the oocyte-to-embryo transition. Functionally, ZAR1 mediates formation of MARDO (mitochondria-associated ribonucleoprotein domain), a membraneless compartment that stores maternal mRNAs in oocytes 1. ZAR1 undergoes liquid-liquid phase separation upon binding to the 3'-UTR of maternal mRNAs, assembling MARDO around mitochondria in response to increased mitochondrial membrane potential during oocyte growth 1. Stored maternal mRNAs in MARDO are translationally repressed, and loss of ZAR1 disrupts this compartment, causing premature mRNA loss and dispersed mitochondrial distribution 1. Beyond mRNA storage, ZAR1 regulates oocyte epigenetic maturation by binding transcripts encoding histone modifiers and controlling their stability and translation, essential for proper zygotic genome activation 2. Clinically, ZAR1 mutations cause primary infertility through defective oocyte maturation and early embryonic arrest 3. Pathogenic variants disrupt either MARDO localization (V118A) or RNA-binding capability (R397Q, S121*), impairing maternal mRNA storage 3. ZAR1 variants contribute significantly to premature ovarian insufficiency (POI) 4, and ZAR1 expression declines with advancing maternal age, correlating with age-related oocyte quality decline 2. Additionally, ZAR1 functions in ovarian somatic cells to suppress apoptosis and mitophagy, with therapeutic potential for POI treatment 5.