Human MCFD2 (multiple coagulation factor deficiency 2) is a 16-kDa protein known to participate in the transport of the glycosylated human coagulation factors V and VIII along the secretory pathway. MCFD2, a binding partner of lectin mannose-binding 1 (LMAN1), causes combined deficiencies of coagulation factors V and VIII. MCFD2 promotes cancer metastasis by regulating LMAN1 and LGALS3BP expression levels. Hence, MCFD2 may represent a promising candidate for a novel therapeutic target for patients with metastatic OSCCs. MCFD2 is an EF-hand domain protein that forms a calcium-dependent heteromeric complex with LMAN1 in cells. Missense mutations in the EF-hand domains of MCFD2 abolish the interaction with LMAN1. The LMAN1-MCFD2 complex may serve as a cargo receptor for the ER-to-Golgi transport of FV and FVIII, and perhaps some other glycoproteins. The B domain of FVIII may be important in mediating its interaction with the LMAN1-MCFD2 complex.