Several interrelated mechanisms have been proposed to contribute to altered Ca2+ homeostasis in muscular dystrophy including (1) enhanced trans-sarcolemmal Ca2+ entry (Michelucci et al., 2018; Zabłocka et al., 2021; Mareedu et al., 2021), (2) increased RyR1 Ca2+ leak (Bellinger et al., 2009; Andersson et al., 2012), (3) impaired SR Ca2+ reuptake (Viner et al., 1996; Sharov et al., 2006; Dremina et al., 2007), (4) increased oxidative stress (Whitehead et al., 2008; Petrillo et al., 2017), and (5) mitochondrial dysfunction (Mareedu et al., 2021; Budzinska et al., 2021). The gene discussed is RYR1; the disease is muscular dystrophy.