The sarcoplasmic reticulum (SR) of striated muscle is a highly specialized intracellular membrane system that plays a key role in the contraction-relaxation cycle of muscle. Its primary function is the regulation of cytoplasmic Ca2+ concentration. A key element in this regulation is the Sarco(endo)plasmic reticulum Ca2+-adenosine triphosphatase (SERCA), which by sequestering Ca2+ into the SR, induces and maintains relaxation. It has been extensively studied with respect to structure and mechanism of action, and more recently to gene expression. Three separate genes encode five SERCA isoforms, two of which, SERCA 1 and SERCA 2, are expressed in skeletal muscle. In the first part of this review we focus on the general properties of the Ca2+ pump (structure and function and regulation of activity). In the second part we describe variations in SERCA expression in various physiological and pathological situations. These have essentially been studied in the heart and skeletal muscles, with data in respiratory muscles being very limited.