ARMCX3 is an X-linked armadillo repeat-containing protein that functions as a key regulator of mitochondrial dynamics and neuronal metabolism. Mechanistically, ARMCX3 localizes to mitochondria and regulates mitochondrial trafficking in neurons by interacting with the Kinesin/Miro/Trak2 motor complex in a calcium-dependent manner 1. The protein controls mitochondrial aggregation and transport along axons, linking mitochondria to molecular motor systems essential for neuronal energy supply 1. Beyond mitochondrial function, ARMCX3 regulates reactive oxygen species (ROS) signaling in dental pulp stem cells and acts as a negative regulator of adipose tissue browning, suppressing thermogenic gene expression and mitochondrial oxidative activity 23. Clinically, ARMCX3 shows relevance to multiple disease states. Rare variants in ARMCX3 are associated with sleep-disordered breathing phenotypes 4, and the gene functions as a crosstalk factor linking periodontitis and osteoporosis through pyroptosis-related pathways and MAPK signaling 5. ARMCX3 expression is elevated in drug-induced senescent melanoma cells, suggesting potential therapeutic targeting 6. Additionally, viral pathogens exploit ARMCX3 regulation; Epstein-Barr virus-encoded non-coding RNAs downregulate ARMCX3 mRNA to facilitate viral replication 7. DNA methylation changes in ARMCX3 are associated with metabolic dysfunction in low birth weight individuals 8.