MCOLN2 (mucolipin-2/TRPML2) is an endolysosomal cation channel that functions as a Ca²⁺-permeable, inwardly rectifying ion channel 1 also permeable to Na⁺, Fe²⁺, and Mg²⁺ 2. The channel is primarily expressed in immune cells, particularly lymphocytes 1, localizing to lysosomes, late endosomes, recycling endosomes, and the plasma membrane 1. MCOLN2 is activated by PI(3,5)P2 and sulfonamide-related chemicals 1. Mechanistically, MCOLN2 regulates calcium release from endolysosomes to mediate vesicle fusion and trafficking events 1. In B-lymphocytes, MCOLN2 and MCOLN1 play redundant roles in specialized lysosomal function 1. The channel promotes viral entry by enhancing trafficking efficiency through endosomal compartments for enveloped RNA viruses 3. Clinically, MCOLN2 dysregulation contributes to disease progression: it is upregulated in prostate cancer, promoting proliferation and migration via IL-1β/NF-κB signaling 4, and restricts Salmonella Typhi replication through magnesium-mediated nutritional immunity 5. Conversely, MCOLN2 enhances replication of certain viruses as part of the type I interferon response 6. MCOLN2 also regulates macrophage phenotype switching via calcium-dependent TFEB activation 7, suggesting immunotherapeutic potential.