The article "Reducing the Environmental Sensitivity of Yellow Fluorescent Protein: Mechanism and Applications" by Oliver Griesbeck, Geoffrey S. Baird, Robert E. Campbell, David A. Zacharias, and Roger Y. Tsien, published in *J. Biol. Chem.*, discusses the development and applications of a new variant of yellow fluorescent protein (YFP) called Citrine. Citrine, derived from random mutagenesis and screening in *Escherichia coli*, exhibits several improvements over previous YFPs, including reduced pH sensitivity, chloride interference, enhanced photostability, and better expression at 37°C. The Q69M mutation in Citrine confers these benefits by filling a halide-binding cavity adjacent to the chromophore, preventing halide binding and reducing pH sensitivity. The authors also describe the construction of improved calcium indicators by inserting calmodulin into Citrine or fusing it with other proteins, which have been used to study calcium dynamics in various cellular compartments, including the Golgi apparatus. The x-ray structure of Citrine reveals the structural basis for these improvements, providing insights into the mechanism of the Q69M mutation. Overall, Citrine is a significant advancement in the field of genetically encoded indicators for monitoring protein interactions and cellular processes.The article "Reducing the Environmental Sensitivity of Yellow Fluorescent Protein: Mechanism and Applications" by Oliver Griesbeck, Geoffrey S. Baird, Robert E. Campbell, David A. Zacharias, and Roger Y. Tsien, published in *J. Biol. Chem.*, discusses the development and applications of a new variant of yellow fluorescent protein (YFP) called Citrine. Citrine, derived from random mutagenesis and screening in *Escherichia coli*, exhibits several improvements over previous YFPs, including reduced pH sensitivity, chloride interference, enhanced photostability, and better expression at 37°C. The Q69M mutation in Citrine confers these benefits by filling a halide-binding cavity adjacent to the chromophore, preventing halide binding and reducing pH sensitivity. The authors also describe the construction of improved calcium indicators by inserting calmodulin into Citrine or fusing it with other proteins, which have been used to study calcium dynamics in various cellular compartments, including the Golgi apparatus. The x-ray structure of Citrine reveals the structural basis for these improvements, providing insights into the mechanism of the Q69M mutation. Overall, Citrine is a significant advancement in the field of genetically encoded indicators for monitoring protein interactions and cellular processes.