This dataset profiles the proteomic effects of altering BAP1 expression in human trophoblast stem cells and trophoblast organoids. Samples from control, BAP1-overexpressing, and BAP1-knockdown conditions were analyzed by LC–MS/MS. DIA-NN–based quantification and differential analysis revealed BAP1-dependent changes affecting trophoblast differentiation, inflammatory signaling, and pathways linked to early-onset preeclampsia.