LMAN1 (lectin, mannose binding 1) functions as a cargo receptor protein that facilitates endoplasmic reticulum (ER)-to-Golgi transport of specific secreted proteins 1. LMAN1 forms a heterodimeric complex with MCFD2 at 1:1 stoichiometry, serving as the primary cargo receptor for coagulation factors V and VIII (FV/FVIII) 2. The protein cycles between the ER and ER-Golgi intermediate compartment, with its cytoplasmic domain containing COPII binding motifs that enable packaging into transport vesicles 3. Mechanistically, LMAN1 primarily serves as a shuttling carrier for MCFD2, which appears to carry out the actual cargo binding function through calcium-dependent protein-protein interactions with the B domain of FVIII 42. While LMAN1 is a mannose-specific lectin, carbohydrate binding is not essential for FV/FVIII transport 4. LMAN1 deficiency causes combined factor V and VIII deficiency (F5F8D), a bleeding disorder characterized by reduced plasma levels of both coagulation factors 5. In LMAN1-deficient mice, FV and FVIII levels are reduced to approximately 50% of normal, with accumulation of proteins like α1-antitrypsin in the ER 5. Beyond coagulation, LMAN1 has been implicated in glioma progression and may serve as a receptor for house dust mite allergens 67.