EMC10 encodes a component of the endoplasmic reticulum membrane protein complex (EMC) that facilitates energy-independent insertion of membrane proteins into ER membranes, particularly those with weakly hydrophobic transmembrane domains or destabilizing features 1. The protein exists in two functionally distinct isoforms: a membrane-bound form (mEMC10) that suppresses hepatic ER stress and a secreted form (scEMC10) that regulates metabolic homeostasis 2. The secreted isoform acts as a circulating inhibitor of thermogenesis by binding to PKA catalytic subunit and inhibiting CREB signaling, while also suppressing muscle glucose uptake through downregulation of GLUT4 expression and membrane translocation 34. Clinically, scEMC10 is elevated in human obesity and positively correlates with insulin resistance 3. Biallelic loss-of-function variants in EMC10 cause a neurodevelopmental disorder characterized by intellectual disability, language impairment, and dysmorphic facial features 56. Recent studies indicate EMC10 variants may exhibit dual molecular effects, presenting either as mild-to-moderate intellectual disability without neurological findings or as severe disability with hypotonia and gait abnormalities 7. Therapeutic targeting of scEMC10 through neutralizing antibodies shows promise for treating obesity and metabolic disorders 3.