1.A.106 The Calcium Load-activated Calcium Channel (CLAC) Family 

Maintaining homeostasis of Ca²⁺ stores in the endoplasmic reticulum (ER) is crucial for proper Ca²⁺ signaling and key cellular functions. The Ca²⁺-release-activated Ca²⁺ (CRAC) channel is responsible for Ca²⁺ influx and refilling after store depletion. Transmembrane and coiled-coil domains protein 1 (TMCO1) is an ER transmembrane protein with 3 TMSs that actively prevents Ca²⁺ stores from overfilling, acting as a 'Cacium Load-activated Calcium channel' or 'CLAC' channel. TMCO1 undergoes reversible homotetramerization in response to ER Ca²⁺ overloading and disassembly upon Ca²⁺ depletion and forms a Ca²⁺-selective ion channel in liposomes. TMCO1 knockout mice reproduce the main clinical features of human cerebrofaciothoracic (CFT) dysplasia spectrum, a developmental disorder linked to TMCO1 dysfunction, and exhibit severe mishandling of ER Ca²⁺ in cells. Thus, TMCO1 provides a protective mechanism to prevent overfilling of ER stores with calcium ions (Wang et al. 2016).  The CLAC Family was formerly the DUF106 Family.