{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nVPS33A is a key Sec1/Munc18 (SM) family protein that serves as an essential subunit of the homotypic fusion and vacuole protein sorting (HOPS) complex. It is critical for orchestrating membrane tethering and fusion between endosomes, autophagosomes, and lysosomes—a process fundamental to maintaining proper cellular homeostasis. Structural and functional investigations have revealed that VPS33A is recruited to the HOPS complex via interaction with VPS16 and modulates SNARE‐mediated membrane fusion, including interactions with syntaxin 17 that may be regulated by a phosphoserine “master switch.” In addition, post‐transcriptional regulation by microRNAs has been shown to target VPS33A, thereby influencing autophagosome–lysosome fusion, which is underscored by findings that impaired fusion leads to autophagosome accumulation and cellular toxicity."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic studies have highlighted that mutations in VPS33A lead to a wide spectrum of disorders caused by defective vesicular trafficking and lysosomal dysfunction. In mice, a mutation in Vps33a results in a phenotype that resembles human Hermansky–Pudlak syndrome, while comparative analyses have distinguished functionally divergent VPS33 homologues, with VPS33A generally fulfilling tissue‐specific roles. In humans, missense mutations in VPS33A have been linked to mucopolysaccharidosis‐like presentations and novel multisystem diseases that feature abnormal lysosomal acidification, glycosaminoglycan accumulation, and impaired formation of the HOPS and CORVET complexes. These findings underscore the importance of intact VPS33A function for the proper biogenesis of intracellular organelles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "9"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its fundamental cellular role, modulation of VPS33A activity holds significant therapeutic promise. In tuberculosis, up‐regulation of specific microRNAs—such as miR-423-5p—leads to VPS33A suppression and subsequent inhibition of autophagosome–lysosome fusion, thereby influencing the host’s ability to clear infections. Furthermore, in melanoma cells, depletion of VPS33A disrupts protein trafficking and melanosome maturation, resulting in increased nuclear accumulation of chemotherapeutic agents and enhanced treatment sensitivity. Collectively, these studies position VPS33A as a central regulator of intracellular fusion events with broad implications in disease pathogenesis and therapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lena Wartosch, Ufuk Günesdogan, Stephen C Graham, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Elevated pulmonary tuberculosis biomarker miR-423-5p plays critical role in the occurrence of active TB by inhibiting autophagosome-lysosome fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Emerg Microbes Infect (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/22221751.2019.1590129"}], "href": "https://doi.org/10.1080/22221751.2019.1590129"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30898038"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30898038"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tamio Suzuki, Naoki Oiso, Rashi Gautam, et al. 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