This experiment describes a quantitative proteomic analysis of whole-cell lysates from induced neurons (iN) and induced dopaminergic neurons (iDA) differentiated from human embryonic stem cells of three genotypes: control, ASAH1 knockout, and SMPD1 knockout. Triplicate biological samples were prepared and analyzed using TMTpro 18-plex labeling coupled to high-resolution Orbitrap mass spectrometry with FAIMS. Data were processed with target-decoy database searching, stringent FDR control, and reporter ion–based quantification. The resulting dataset enables comparative profiling of proteomic alterations associated with lysosomal dysfunction and neurodegeneration-relevant pathways in distinct neuronal subtypes.