TMED2 is a transmembrane cargo receptor protein essential for protein trafficking through the early secretory pathway. TMED2 functions as a dual-sided receptor: recognizing cargo at the ER lumen while coordinating vesicle coat formation at the cytoplasm 1. In COPII-mediated anterograde transport, TMED2 selectively transports GPI-anchored proteins and associates with TMED10 as co-receptors 1. TMED2 also regulates GPCR trafficking, controlling exocytic transport of receptors like F2RL1 and OPRM1 to the plasma membrane 1. Additionally, TMED2 and TMED10 operate as a supercomplex controlling lipid exchange at ER-Golgi contact sites, regulating cholesterol and ceramide distribution critical for plasma membrane nanodomain formation 2. Under ER stress, TMED2 participates in Golgi-independent unconventional secretion of transmembrane proteins including CFTR and SARS-CoV-2 Spike protein 3. Clinically, TMED2 dysfunction causes uromodulin trafficking defects linked to autosomal dominant tubulointerstitial kidney disease; pharmacological TMED targeting rescues mutant protein trafficking and mitigates kidney damage 1. TMED2 is upregulated in multiple cancers including cervical cancer and glioma, correlating with poor prognosis and promoting tumor cell proliferation and invasion 45. TMED2 also regulates proinsulin processing in pancreatic β-cells through lipid binding interactions, relevant to type 2 diabetes pathogenesis 6.