Proposed interactions of NBEAL2 with SEC22B and P-selectin during α-granule biogenesis. The ER extends throughout MKs, making numerous contacts with the Golgi, organelles, early endosomes, late endosomes/multivesicular bodies (MVB), and other vesicles. α-granule biogenesis likely begins with events at the trans-Golgi network mediated by the VPS33B/VPS16B complex and proceeds via maturation of endosomes into α-granules containing the membrane spanning protein P-selectin. We showed previously that NBEAL2 can bind to P-selectin and that these proteins likely interact on precursor and/or mature α-granules to stabilize their protein cargo.³⁵  We show in this study that NBEAL2 can simultaneously bind to SEC22B and present evidence this interaction may be required for α-granule formation. A possible implication of these interactions is that NBEAL2 acts as a bridge between the ER and forming/mature α-granules that is necessary for granule production and/or cargo retention.