1. Many biological processes that are governed by intracellular calcium signals 
rely on intracellular stores, which provide a reliable, controlled release of 
calcium into the cytoplasm. Calcium release through the ryanodine receptor 
(RyR), the main ion channel in the sarcoplasmic reticulum (the calcium store in 
muscle) is the key determinant of muscle force. 2. Calsequestrin, the main 
calcium buffer in the sarcoplasmic reticulum, provides a pool of calcium for 
release through the RyR and acts as a luminal calcium sensor for the channel via 
its interactions with triadin and junctin. Until recently, how calsequestrin 
communicated the store Ca(2+) load to the RyR remained unknown. 3. Calsequestrin 
1 (skeletal calsequestrin) has been shown to both inhibit and activate the 
skeletal RyR1, dependent on whether it's bound to the RyR1 directly or 
indirectly via anchoring proteins. 4. The phosphorylation status of 
calsequestrin 1 is deemed important: it influences the Ca(2+) binding capacity 
of calsequestrin, the way in which calsequestrin 1 regulates the RyR1 and how 
calsequestrin 1 interacts with the key anchoring protein junctin. 5. In skeletal 
muscle, junctin plays a more critical role than triadin in the mechanism that 
controls Ca(2+) release from the sarcoplasmic reticulum. 6. The close 
relationship between altered expression and dysfunction of calsequestrin in 
several skeletal and cardiac disorders highlights the critical role that 
calsequestrin plays in maintaining Ca(2+) homeostasis and regulation of muscle 
contraction.