The article discusses the functional roles of endoplasmic reticulum (ER)–mitochondria contacts in eukaryotic cells. These contacts are crucial for coordinating the functions of the two organelles, including lipid synthesis, calcium signaling, and mitochondrial biogenesis and trafficking. The ER and mitochondria form close physical contacts, which are essential for their coordinated activities. These contacts are maintained despite the dynamic nature of both organelles, as they move along the cytoskeleton and maintain their structural integrity. ER–mitochondria contacts are involved in lipid exchange, where enzymes involved in lipid biosynthesis are localized at these sites. The ER-associated membrane (MAM) is enriched in enzymes that facilitate lipid synthesis, including phosphatidylserine synthase. A complex called ERMES has been identified in yeast, which may coordinate phospholipid synthesis between the ER and mitochondria. ERMES components include both ER and mitochondrial proteins, and its disruption affects lipid exchange. ER–mitochondria contacts also play a role in mitochondrial division, where the ER helps to constrict mitochondria before the division machinery is recruited. The ER marks the sites where mitochondrial division occurs and maintains contact even after division. The protein Mmm1, part of the ERMES complex, is involved in this process. Additionally, the ER is involved in mitochondrial fusion, with proteins like MFN2 tethering mitochondria to the ER. ER–mitochondria contacts are also important for calcium signaling, as the ER releases calcium to the mitochondria, which is essential for mitochondrial function and apoptosis. The calcium release is mediated by the inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P3R) and voltage-dependent anion-selective channel protein 1 (VDAC1). The ER and mitochondria form localized calcium transfer sites, which are crucial for maintaining calcium homeostasis. The article also discusses the dynamic nature of ER and mitochondrial movements, with both organelles moving along microtubules in animal cells. The ER protein MIRO is involved in mitochondrial movement and calcium sensing, and its localization at ER–mitochondria contacts suggests a role in coordinating these processes. The ER and mitochondria also have coupled dynamics in yeast, with both organelles being inherited into the bud and maintaining contact during cell division. In conclusion, ER–mitochondria contacts are essential for the coordinated functions of these two organelles, including lipid synthesis, calcium signaling, and mitochondrial dynamics. Understanding the molecular mechanisms that regulate these contacts is crucial for elucidating the roles of these organelles in cellular processes and disease.The article discusses the functional roles of endoplasmic reticulum (ER)–mitochondria contacts in eukaryotic cells. These contacts are crucial for coordinating the functions of the two organelles, including lipid synthesis, calcium signaling, and mitochondrial biogenesis and trafficking. The ER and mitochondria form close physical contacts, which are essential for their coordinated activities. These contacts are maintained despite the dynamic nature of both organelles, as they move along the cytoskeleton and maintain their structural integrity. ER–mitochondria contacts are involved in lipid exchange, where enzymes involved in lipid biosynthesis are localized at these sites. The ER-associated membrane (MAM) is enriched in enzymes that facilitate lipid synthesis, including phosphatidylserine synthase. A complex called ERMES has been identified in yeast, which may coordinate phospholipid synthesis between the ER and mitochondria. ERMES components include both ER and mitochondrial proteins, and its disruption affects lipid exchange. ER–mitochondria contacts also play a role in mitochondrial division, where the ER helps to constrict mitochondria before the division machinery is recruited. The ER marks the sites where mitochondrial division occurs and maintains contact even after division. The protein Mmm1, part of the ERMES complex, is involved in this process. Additionally, the ER is involved in mitochondrial fusion, with proteins like MFN2 tethering mitochondria to the ER. ER–mitochondria contacts are also important for calcium signaling, as the ER releases calcium to the mitochondria, which is essential for mitochondrial function and apoptosis. The calcium release is mediated by the inositol 1,4,5-trisphosphate receptor (Ins(1,4,5)P3R) and voltage-dependent anion-selective channel protein 1 (VDAC1). The ER and mitochondria form localized calcium transfer sites, which are crucial for maintaining calcium homeostasis. The article also discusses the dynamic nature of ER and mitochondrial movements, with both organelles moving along microtubules in animal cells. The ER protein MIRO is involved in mitochondrial movement and calcium sensing, and its localization at ER–mitochondria contacts suggests a role in coordinating these processes. The ER and mitochondria also have coupled dynamics in yeast, with both organelles being inherited into the bud and maintaining contact during cell division. In conclusion, ER–mitochondria contacts are essential for the coordinated functions of these two organelles, including lipid synthesis, calcium signaling, and mitochondrial dynamics. Understanding the molecular mechanisms that regulate these contacts is crucial for elucidating the roles of these organelles in cellular processes and disease.