Collectively, our results suggest that Munc13-4’s role in resting cancer cells involves endosomal remodeling to generate secretion-competent MVBs using Ca2+ increases originating either from the endosomal structures (Ghislat and Knecht, 2013; He et al., 2016) or from increased cytosolic Ca2+ from Orai1 Ca2+ channels that are essential for metastasis (Yang et al., 2009; Feng et al., 2010) and required for enhanced exosome release (Didiasova et al., 2015). This evidence concerns the gene UNC13D and cancer.