This is a review of ten previously published studies of the human sperm proteome. Proteins expressed on the sperm cell surface were identified and characterized by a combination of vectorial labelling with radioiodine and biotin, PI-PLC treatment, two-dimensional gel electrophoresis, immuno and lectin blotting procedures, affinity overlay assays with radioactive nucleotide triphosphates and 45Ca, and mass spectrometry analysis. Examination of capacitation-induced modifications of the human sperm proteome led to the cloning and characterisation of two new phospho-regulated cancer-testis antigens, which we named Fibrous Sheath Protein 95 (FSP95) and CABYR (calcium-binding tyrosine phosphorylation regulated). A protein kinase A RII binding domain is present between amino acids 124 and 141 identifying FSP95 (now commonly known as AKAP3) as a member of the A kinase anchoring protein-family which provides spatial and temporal specificity to the cAMP-PKA pathway. In addition to scaffolding PKA, PDE and protein phosphatases, AKAPs also bind to a group of four proteins that share homology to the RII dimerization/docking (R2D2) domain of PKA' regulatory subunit. CABYR, which is one of these four proteins, also interacts with a diverse array of signal tranducers via its SH3-, R2D2-, and proline-rich extension-like domains. AKAP3 and CABYR appear to associate in high molecular weight multi-protein complexes, which regulate the flagella' energy supply and movements. Diagonal gel electrophoresis experiments suggest that the high molecular weight signal-integrating scaffold partly is established by homo- and hetero-oligomerization of lower molecular weight splice variants of CABYR. The putative role of CABYR in lung cancer cells is finally discussed.