Fibronectin type III and SPRY domain-containing protein 2 (FSD2)

Fibronectin type III and SPRY domain-containing protein 2 (FSD2), also known as minispryn, is a muscle-expressed protein containing fibronectin type III and SPRY domains[1][3][4]. It belongs to the FN3/SPRY family and is a paralog of myospryn (CMYA5), sharing significant sequence similarity in its C-terminal region. FSD2 is expressed predominantly in cardiac and skeletal muscle, where it is a component of the so-called myospryn complex, comprising myospryn (CMYA5), minispryn (FSD2), and the ryanodine receptor (RyR1 in skeletal muscle/RyR2 in heart)[2][4]. Immunoaffinity and co-immunoprecipitation experiments indicate that these proteins interact, especially at the junctional sarcoplasmic reticulum, contributing to triad (skeletal) or dyad (cardiac) architecture[2][4]. In animal models, loss of function or mutation in complex partners can contribute to myopathy and cardiac dysfunction due to disorganization of these critical protein assemblies[2]. While FSD2 has not been identified as a classic therapeutic target (receptor, enzyme, ion channel, etc.), its role as a structural and scaffolding protein is emerging in muscle physiology and pathology[1][2][4][5].

Other names

minisprynSPRYD1RP11-127F21SPRY domain-containing protein 1