ATP2B4 (also known as PMCA4) belongs to the IIB subfamily of P-type ATPases, whose members are plasma membrane Ca2+ ATPases (PMCAs) that catalyse the hydrolysis of ATP coupled with the transport of calcium []. PMCAs play important roles for the regulation of bone homeostasis in both mice and humans by modulating Ca(2+) signalling in osteoclasts [].ATP2B4 is is expressed at high levels in numerous tissues/cell types, including the brain, the heart, and the spermatozoa []. The C-terminal of ATP2B4 interacts with the PDZ domains of a number of partner proteins, including neuronal nitric-oxide synthase (nNOS) []. The interaction between ATP2B4 and neuronal nitric-oxide synthase regulates cardiac contractility through modulation of a compartmentalised cyclic nucleotide microdomain []. ATP2B4 is highly concentrated in the spermatozoon head and is involved in the fertilisation process []. It also has a role in colon cancer tumourigenesis [].