The large dense-core vesicle (LDCV), a type of lysosome-related organelle, is involved in the secretion of hormones and neuropeptides in specialized secretory cells. The granin family is a driving force in LDCV biogenesis, but the machinery for granin sorting to this biogenesis pathway is largely unknown. The mu mutant mouse, which carries a spontaneous null mutation on the Muted gene (also known as Bloc1s5) that encodes a subunit of lysosome-related organelles complex-1 (BLOC-1), is a mouse model of Hermansky-Pudlak syndrome. We here found that LDCVs were enlarged in muadrenal chromaffin cells. Chromogranin A (CgA) was increased in mu adrenals and muted-knockdown cells. The increased CgA in mu mice was likely due to the failure of its sorting-out, which impairs LDCV maturation and docking. Inmu chromaffin cells, the size of readily releasable pool and the vesicle release frequency were reduced. Our studies suggest that the muted protein is involved in the sorting-out of CgA during the biogenesis of LDCVs.