TMEM184 proteins are Ca(2+) uptake transporters in lysosomes.

TMEM184 family proteins function as lysosomal Ca2+ uptake transporters, selectively transporting Ca2+ and refilling lysosomal stores essential for lysosomal signaling and homeostasis.

• Why it matters: Lysosomal Ca2+ release depends on replenishment, but the molecular identity of the Ca2+ uptake conduit in lysosomes has been unclear.
• What they did: Using a Ca2+-imaging-based genetic screen of the lysosomal membrane proteome, the study identified TMEM184 family proteins as LyCaTs and tested Ca2+ selectivity and lysosomal phenotypes after TMEM184B/C loss.
• The result: TMEM184B/C depletion depleted lysosomal Ca2+ stores, reduced Ca2+ release, and disrupted lysosomal exocytosis, biogenesis, and membrane repair, phenocopying TRPML1 deficiency; a human TMEM184B neurodevelopmental mutation impaired transport and Tmem184b-deficient mice showed profound motor impairment.

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