Highlights d Human TRPML2 extracytosolic/lumenal domain (ELD) structures at pH 4.5 and 6.5 d Comparison of the three human TRPML channel ELDs at acidic and near-neutral pH d Ca 2+ interacts with the TRPML2 acidic pre-pore loop in a pHdependent manner d Ca 2+ and pH do not influence ELD structure but play a role in oligomer integrity
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