ORAI1 and muscular disease: One striking visual effect that kept our attention was the net tangles, the so-called tubular aggregates (TAs) (Fig. 3A1), quantified in Fig. 3B. These aggregates consist of abnormal sarcoplasmic reticulum (SR) membranes, usually associated with mitochondrial activity impairment and accumulation of oxidative stress by-products in the myofibers12 or with mutations in the stromal-interacting molecule-1 (STIM1) and Ca2+ permeable channel of external membranes, ORAI1 found in several muscle disorders such as TA myopathy (TAM)13.