Mucolipidosis type IV is a poorly understood lysosomal storage disease caused by alterations in the mucolipin lysosomal Ca(2+) channel. In this study, we generated mucolipin-knockout Dictyostelium cells, and observed that lysosome exocytosis was markedly increased in these cells compared with wild-type cells. In addition, mucolipin-knockout cells were more resistant to Ca(2+) deprivation, and the Ca(2+) concentration in their secretory lysosomes was decreased, suggesting that mucolipin transfers Ca(2+) ions from the cytosol to the lumen of secretory lysosomes. We speculate that mucolipin attenuates the fusogenic effect of local cytosolic increases in Ca(2+) by dissipating them into the lumen of lysosomal compartments.