Maintaining homeostasis of Ca2+ stores in the endoplasmic reticulum (ER) is crucial for proper Ca2+ signaling. Calcium load-activated calcium channel, also known as transmembrane and coiled-coil domains 1 (TMCO1), is an ER transmembrane protein that prevents Ca2+ ER stores from overfilling. In response to ER overloading, TMCO1 undergoes reversible homotetramerization and forms a Ca(2+)-selective ion channel [].
