JMY (junction mediating and regulatory protein) is a multifunctional p53 cofactor with dual roles in nuclear transcription and cytoplasmic actin dynamics. In the nucleus, JMY acts as a cofactor that enhances p53-dependent transcription and apoptosis through interaction with p300/EP300, contributing to p53 stress responses such as DNA damage-induced cell death 1. In the cytoplasm, JMY functions as a nucleation-promoting factor for actin filament assembly, activating the Arp2/3 complex to generate branched actin networks while also catalyzing unbranched actin polymerization independently 1. This dual actin-nucleating capacity—combining both Arp2/3-dependent and Arp2/3-independent mechanisms—distinguishes JMY from canonical Wiskott-Aldrich Syndrome family nucleation-promoting factors 2. JMY promotes cell motility through dynamic actin regulation and participates in autophagy by direct recruitment to phagophore membranes via MAP1LC3B during nutrient stress, where it facilitates actin assembly 1. The subcellular localization of JMY determines whether it functions as a p53 transcriptional cofactor or cytoplasmic actin regulator, providing a mechanism for coordinating stress responses with cell migration and remodeling of dynamic membrane structures.