To capture the changes in the lysosomal proteome upon TRPML1 activation, achieved using a small molecule agonist MLSA5, human cancer cells, with or without gene-editing, stably expressing TMEM192-mRFP-3xHA (Lyso-IP), were treated with MLSA5 and Lyso-IP samples were prepared and processed for TMT-MS analysis. Each condition was performed in triplicate.