SYPL2, also known as Mitsugumin 29, was initially identified as a transmembrane protein from the triad junction in skeletal muscle that had significant homology with members of the synaptophysin family. SYPL2 is thought to participate in the excitation-contraction coupling process of skeletal muscle as SYPL2-null mice showed reduced muscle contractile force and altered triad junction structure and increased susceptibility to fatigue of the skeletal muscle. SYPL2 plays a critical role in muscle Ca2+ signaling by regulating the process of store-operated Ca2+ entry and interacts with ryanodine receptor (RyR), thereby influencing intracellular Ca2+ homeostasis through changes in the RyR/Ca2+ release function. Co-expression of SYPL2 and RyR in cultured cells leads to apoptotic cell death resulting from the depletion of Ca2+ from the intracellular stores.