We show here a link between an endolysosomal cation channel, TRPML3, and the development of lung dysfunction and an emphysema-like phenotype in Trpml3−/− mice due to the inability of Trpml3−/− AMΦ to appropriately regulate MMP-12 levels in BALF. The gene discussed is MCOLN3; the disease is pulmonary emphysema.