Skeletal muscle contraction is triggered when a membrane depolarisation induces a massive increase in intracellular calcium concentration. This process called “excitation-contraction (E-C) coupling” relies on a multimolecular protein complex, the calcium release complex (CRC) organized around the sarcoplasmic reticulum calcium channel, the ryanodine receptor (RyR1) in the reticulum membrane and the voltage dependant calcium channel, the dihydropyridine receptor DHPR, in the plasma membrane. Among the proteins involved in the efficient function of the CRC, calsequestrin (CSQ), triadin and junctin are sarcoplasmic reticulum proteins able to interact with RyR1 and regulate calcium release. A similar complex exists in cardiac muscle, but with cardiac specific isoforms (RyR2, CSQ2 …).Triadin is a multiprotein family and the different isoforms could have different functions. Whereas the two main skeletal muscle isoforms, Trisk 95 and Trisk 51, are specifically localized in the skeletal muscle triad where they are associated to RyR1, Trisk 32, a cardiac and skeletal muscle isoform, is localized in skeletal muscle not only in the triad but in the whole reticulum, and regulates calcium releases via IP3R. In order to identify the function of triadin, triadin KO mice lines have been developed. These mice have both skeletal muscle and cardiac defects. Based on the phenotype of these mice, we search for mutation in the triadin gene in patients with a rare cardiac disease, Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT), and without mutation identified in the classical genes related to this disease, the cardiac ryanodine receptor RYR2 and the cardiac calsequestrin CASQ2. We identified the first mutations in the TRDN gene, and demonstrated that these mutations resulted in the absence of protein, therefore the patients are all natural triadin KO. To further understand the function of triadin, we expressed triadin in a non muscle cell line, and observed that this expression resulted in modification of the endoplasmic reticulum, associated with an alteration of the microtubule network. We identified the amino acids responsible of this effect. Our current hypotheses for the functions of triadin are i) anchoring of CSQ to the triad, ii) anchoring of the reticulum to the microtubule network and iii) alteration of membrane curvature allowing RyR-DHPR contact.