MIGA2 (mitoguardin 2) is a mitochondrial outer membrane protein that functions as a critical regulator of organellar interactions and cellular energy metabolism. Primary function: MIGA2 regulates mitochondrial fusion by forming homo- and heterodimers at the mitochondrial outer membrane and facilitating PLD6/MitoPLD dimer formation, thereby promoting mitochondrial fusion and clustering 1. Beyond fusion, MIGA2 establishes functional bridges between multiple organelles—linking mitochondria to lipid droplets (LDs) and the endoplasmic reticulum (ER) through binding to VAP-A/VAP-B proteins via an amphipathic LD-targeting motif 2. Mechanism: MIGA2 couples de novo lipogenesis in mitochondria to triglyceride synthesis in the ER, facilitating efficient lipid storage in LDs 2. In ovarian granulosa cells, MIGA2 regulates proliferation by activating AKT and modulating the Hippo-YAP1 signaling pathway, while also interacting with the steroidogenic acute regulatory protein (StAR) to influence steroid hormone synthesis 34. Disease relevance: MIGA2 expression correlates with hyperandrogenism in polycystic ovary syndrome (PCOS), where increased MIGA2 promotes abnormal steroidogenesis 4. Excessive ER-mitochondria contacts mediated by MIGA2 can contribute to neurodegeneration 5. Clinical significance: MIGA2's role in lipid homeostasis, steroid metabolism, and mitochondrial dynamics suggests broad relevance to metabolic and reproductive endocrine diseases 2.