TMCO1 is a transmembrane endoplasmic reticulum protein with dual roles in calcium homeostasis and protein synthesis. As an ER calcium-selective channel, TMCO1 prevents intracellular Ca2+ store overfilling by assembling into homotetramer complexes that facilitate Ca2+ release in response to ER calcium loading 1. Beyond this channel function, TMCO1 is a critical component of the multi-pass translocon (MPT) complex, which mediates insertion of multi-pass membrane proteins into the ER lipid bilayer following SEC61-mediated insertion of initial transmembrane segments 23. TMCO1 dysfunction is implicated in multiple diseases. Biallelic loss-of-function TMCO1 variants cause craniofacial dysmorphism, skeletal anomalies, and impaired intellectual development syndrome-1 (CFSMR1), characterized by developmental delay, distinctive facial features, and vertebral/rib malformations 4. Non-coding genetic variants near TMCO1 generate >2-fold differences in glaucoma risk among individuals 5, with the rs4656461 risk allele associated with 4-5 year earlier POAG diagnosis 6. TMCO1 is also dysregulated in malignancies: upregulation promotes glioma and ovarian cancer progression through EMT induction and calcium signaling 78, while in glaucomatous trabecular meshwork, TMCO1 drives ferroptosis and extracellular matrix deposition via ERK1/2 signaling 9.