This quantitative proteomic analysis of lysosome-enriched fractions isolated by immunoprecipitation (LysoIP) from HeLa cells expressing TMEM192-3xHA, untagged controls, and ASAH1 knockout lines. Triplicate biological replicates were processed using TMTpro 18-plex labeling and high-resolution Orbitrap mass spectrometry with FAIMS. Data were searched against the human proteome with stringent FDR filtering and reporter ion quantification, enabling comparative profiling of lysosomal protein composition and changes associated with ASAH1 deficiency.