ProAKAP4 as a potential biomarker of fertility and sperm freezability in males of different species - A review

In recent years, special attention has been paid to proAKAP4, the precursor of A-kinase anchoring protein 4 (AKAP4), which plays a crucial role in the structure and function of the sperm flagellum. This testis-specific protein forms the fibrous sheath and local signal transduction required for proper sperm capacitation and motility. Highly conserved across species, proAKAP4 levels are strongly correlated with fertility and sperm survivability post-thaw. This review summarizes the biological roles of proAKAP4 and its potential as a semen quality biomarker in various mammalian species, including humans, horses, bulls, boars, dogs, rodents and other species. We discuss structural and molecular aspects of proAKAP4 (e.g., prodomain, PKA interactions, phosphorylation sites), as well as its involvement in key signaling pathways controlling sperm movement, such as the cAMP-PKA cascade and calcium signaling. The review also outlines various methods for measuring proAKAP4, such as ELISA, Western blotting and immunocytochemistry. Particular attention is given to commercial assays, which allow rapid and species-specific quantification of proAKAP4, independent of seminal plasma or cryoprotectant presence. Although the data are promising, researchers highlight the need for further validation in larger populations under varying environmental conditions. Nonetheless, current findings suggest that proAKAP4 may emerge as a standard marker in andrological diagnostics and a valuable tool for selecting breeding males and optimizing semen cryopreservation procedures.