A proteomic analysis of a eukaryotic cilium was conducted using mass spectrometry to identify proteins in purified flagella from the green alga Chlamydomonas reinhardtii. A total of 360 proteins were identified with high confidence, and 292 more with moderate confidence, indicating a comprehensive dataset. The flagellar proteome is rich in motor and signal transduction components, and contains numerous proteins with homologues associated with diseases such as cystic kidney disease, male sterility, and hydrocephalus in humans and model vertebrates. The results indicate that flagella are far more complex than previously estimated. The study identified 360 proteins by five or more peptides, and 292 proteins by two to four peptides. These proteins include motor proteins, signal transduction proteins, proteins with predicted coiled-coil domains, and predicted membrane proteins. The dataset contains nearly all known flagellar proteins, with only a few exceptions. The results suggest that the flagellar proteome is highly complex and contains many proteins that are conserved in humans but have not been previously characterized in any organism. The study also identified a large number of signal transduction proteins, including 21 protein kinases and 11 protein phosphatases, which are likely to be involved in the control of flagellar motility, signaling, and assembly. The flagellar proteome also contains enzymes involved in nucleotide metabolism and glycolysis, which are essential for flagellar function. The study found that many of these proteins are conserved in humans and Arabidopsis, indicating their importance in ciliary function. The study also identified homologues of vertebrate disease proteins, including polycystin 2 and fibrocystin, which are associated with ciliary dysfunction in human disorders such as polycystic kidney disease. The results suggest that cilia play a critical role in the development of these diseases and that further research is needed to understand their functions and roles in disease. The study highlights the importance of cilia in various biological processes, including motility, sensory perception, and the life cycles of eukaryotes. The findings provide a starting point for future studies to elucidate the roles of these proteins in the assembly and function of cilia and flagella, and to understand why defects in some of these proteins lead to human diseases. The results indicate that cilia and flagella are far more complex than previously believed.A proteomic analysis of a eukaryotic cilium was conducted using mass spectrometry to identify proteins in purified flagella from the green alga Chlamydomonas reinhardtii. A total of 360 proteins were identified with high confidence, and 292 more with moderate confidence, indicating a comprehensive dataset. The flagellar proteome is rich in motor and signal transduction components, and contains numerous proteins with homologues associated with diseases such as cystic kidney disease, male sterility, and hydrocephalus in humans and model vertebrates. The results indicate that flagella are far more complex than previously estimated. The study identified 360 proteins by five or more peptides, and 292 proteins by two to four peptides. These proteins include motor proteins, signal transduction proteins, proteins with predicted coiled-coil domains, and predicted membrane proteins. The dataset contains nearly all known flagellar proteins, with only a few exceptions. The results suggest that the flagellar proteome is highly complex and contains many proteins that are conserved in humans but have not been previously characterized in any organism. The study also identified a large number of signal transduction proteins, including 21 protein kinases and 11 protein phosphatases, which are likely to be involved in the control of flagellar motility, signaling, and assembly. The flagellar proteome also contains enzymes involved in nucleotide metabolism and glycolysis, which are essential for flagellar function. The study found that many of these proteins are conserved in humans and Arabidopsis, indicating their importance in ciliary function. The study also identified homologues of vertebrate disease proteins, including polycystin 2 and fibrocystin, which are associated with ciliary dysfunction in human disorders such as polycystic kidney disease. The results suggest that cilia play a critical role in the development of these diseases and that further research is needed to understand their functions and roles in disease. The study highlights the importance of cilia in various biological processes, including motility, sensory perception, and the life cycles of eukaryotes. The findings provide a starting point for future studies to elucidate the roles of these proteins in the assembly and function of cilia and flagella, and to understand why defects in some of these proteins lead to human diseases. The results indicate that cilia and flagella are far more complex than previously believed.