Formation of calcium entry units. Structural changes from the normal state of a well-loaded SR (left) to a state of Ca²⁺ depletion (right). Depletion leads to the formation of CEUs characterized by longitudinal branches of the transverse tubular system (T-Tubule) and stacks of the longitudinal SR which are connected by STIM1–Orai1 bridges. The right side of the drawing shows the case of Ca²⁺-depleted calsequestrin (CASQ1) in the terminal cisternae. Similar CEUs are now reported as permanent structures in CASQ1-null muscle fibers as means to cope with the compromised Ca²⁺ storing ability. fSR, free (nonjunctional) SR that does not interact with TTs; jSR, junctional SR (terminal cisternae). Figure reproduced from Michelucci et al., 2018, with permission.