Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Within the ER, ERO1A activity increases the concentration of H(2)O(2), which attacks the luminal thiols in ATP2A2 and thus leads to cysteinyl sulfenic acid formation (-SOH) and SEPN1 reduces the SOH back to free thiol (-SH), thus restoring ATP2A2 activity (PubMed:25452428). Acts as a modulator of ryanodine receptor (RyR) activity: protects RyR from oxidation due to increased oxidative stress, or directly controls the RyR redox state, regulating the RyR-mediated calcium mobilization required for normal muscle development and differentiation (By similarity). Essential for muscle regeneration and satellite cell maintenance in skeletal muscle (PubMed:21131290). Interacts with RYR1, RYR2 and RYR3. The N-terminus (first 61 amino acids) contains an endoplasmic reticulum addressing and retention targeting signal. N-glycosylated. Mutant mice show only subtle alterations in the muscle morphology, ultrastructure and contractility. They display increased muscle stress-sensitivity to physical exercise when performed under stress conditions such as a forced swimming test. Under these conditions, they develop muscle atrophy, predominantly affecting trunk muscles and leading to severe kyphosis (PubMed:21858002). The number of satellite cells in uninjured adult muscle is reduced. After one single cardiotoxin-induced injury, a correct restoration of the muscle fibers is seen in skeletal muscle, whereas after two successive injuries, regeneration is completely abolished (PubMed:21131290).