Capacitation is the final stage of spermatozoon maturation which eventually enables it to bind the zona pellucida (ZP) - a thick layer of glycoproteins surrounding the oocyte^1-3. It occurs in the fallopian tubes of the female reproductive tract and is preceded by spermatogenesis (testes) and epididymal maturation (epididymis)^3,4. Capacitation is accompanied by drastic morphological and functional alterations, such as membrane hyperpolarization, changes in membrane lipid composition, intracellular alkalinization, increased level of protein tyrosine phosphorylation by cAMP-dependent PKA, and elevated intracellular concentrations of Ca²⁺ ([Ca²⁺]_i) and pH_i^1,2, which render the sperm chemotaxis-responsive and hyperactive⁶. Increased flagellar bend, triggered by Ca²⁺ signaling, produces asymmetrical, whiplash-like motility pattern that provides the sperm with significantly stronger swimming thrust^1-3. Hyperactivity, together with the eruption of hydrolytic enzymes from the sperm's acrosome vesicle facilitate the disruption of the ZP matrix and make way for the sperm to enter the egg cytoplasm^1-7.  

CatSper (cation channel of spermatozoa) is a sperm-specific Ca²⁺ channel located explicitly in the spermatozoon flagellum². It mediates flagellar hyperactivity⁷, and is chemotactically responsive to progesterone⁸. CatSper is composed of 4 pore-forming subunits (CatSper1-4) with 6 transmembrane (TM) domains each, and of 3 auxiliary subunits: CatSperβ (2 TM domains), CatSperγ and CatSperδ (1 TM domain each)^{1, 2}. While all four CatSper proteins are necessary for the channel's function (and hence male fertility)⁹, each is synthesized independently. Trafficking to the flagellum requires the cooperation of all subunits^1,3.

CatSper1, the first identified subunit of the channel, is highly homologous to Ca_V channels; a voltage sensor domain (S1-S4) containing enough positively charged residues to confer weak voltage sensitivity to the channel². Furthermore, its histidine-rich, intracellular amino terminus likely serves as the pH sensor necessary to induce hyperactivation (by permitting an influx of Ca²⁺)³. Indeed, intracellular alkaline pH (7.9-8.5) was shown to efficiently hyper-activate CatSper channels⁶.