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We have shown the importance of endosomal trafficking proteins in MR1-dependent presentation of <jats:italic>Mycobacterium tuberculosis<\/jats:italic> (Mtb) infection. Two pore channels (TPCs) are endosomal calcium channels that regulate endosomal trafficking. Due to their location on endosomes, we hypothesized that TPCs could be required for MR1-dependent presentation of antigens derived from the intracellular microbe Mtb. We found that TPC1 is critical for the presentation of Mtb infection by MR1; inhibition of TPCs had no effect on MR1 presentation of exogenously delivered antigens, HLA-B presentation, or HLA-II presentation. Finally, we found that the calcium-sensitive trafficking protein Synaptotagmin 7 was also key in the presentation of Mtb infection by MR1. TPC1 and Synaptotagmin 7 may be part of an endosomal pathway by which MR1 can sample intracellular mycobacterial infections.<\/jats:p>","DOI":"10.1371\/journal.ppat.1013342","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T17:39:12Z","timestamp":1754329152000},"page":"e1013342","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Two-pore channels in MR1-dependent presentation of Mycobacterium tuberculosis infection"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7185-5490","authenticated-orcid":true,"given":"Elham","family":"Karamooz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Se-Jin","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessie 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