The study investigates the role of calcineurin in regulating the translocation of dynamin-related protein 1 (Drp1) to mitochondria, which is crucial for mitochondrial fission. Mitochondrial depolarization, induced by agents like thapsigargin and FCCP, triggers a rise in cytosolic Ca2+ levels, activating calcineurin. This activation leads to the dephosphorylation of Drp1 at Serine 637, promoting its translocation to mitochondria and subsequent fission. The subcellular distribution of Drp1 is controlled by the phosphorylation status at Serine 637, with dephosphorylated Drp1 accumulating on mitochondria. Genetic and pharmacological inhibition of calcineurin blocks this process, suggesting that it is a key regulator of mitochondrial fission. The findings highlight the importance of Ca2+/calcineurin-dependent dephosphorylation in controlling mitochondrial morphology and function, particularly in response to mitochondrial dysfunction.The study investigates the role of calcineurin in regulating the translocation of dynamin-related protein 1 (Drp1) to mitochondria, which is crucial for mitochondrial fission. Mitochondrial depolarization, induced by agents like thapsigargin and FCCP, triggers a rise in cytosolic Ca2+ levels, activating calcineurin. This activation leads to the dephosphorylation of Drp1 at Serine 637, promoting its translocation to mitochondria and subsequent fission. The subcellular distribution of Drp1 is controlled by the phosphorylation status at Serine 637, with dephosphorylated Drp1 accumulating on mitochondria. Genetic and pharmacological inhibition of calcineurin blocks this process, suggesting that it is a key regulator of mitochondrial fission. The findings highlight the importance of Ca2+/calcineurin-dependent dephosphorylation in controlling mitochondrial morphology and function, particularly in response to mitochondrial dysfunction.