ORAI2 is a pore-forming subunit of store-operated Ca²⁺ entry (SOCE) channels that assembles with ORAI1 and ORAI3 to form hexameric Ca²⁺ release-activated Ca²⁺ (CRAC) channels 1. Unlike ORAI1, which mediates sustained Ca²⁺ plateaus, ORAI2 generates oscillatory Ca²⁺ patterns and exhibits unique pH sensitivity affecting current amplitude but not inactivation kinetics 2. ORAI2 forms heteromeric channels with ORAI1 that attenuate overall CRAC channel function, thereby fine-tuning SOCE magnitude in T cells and modulating immune responses 1. In disease contexts, ORAI2 demonstrates divergent roles. In Alzheimer's disease models, ORAI2 downregulation potentiates SOCE and decreases amyloid-beta accumulation, suggesting therapeutic potential for rescuing defective Ca²⁺ signaling in neurodegeneration 3. Conversely, in gastric cancer, NSUN2-mediated m5C modification of ORAI2 mRNA increases ORAI2 expression and promotes peritoneal metastasis through enhanced Ca²⁺ signaling in a high-fat microenvironment 4. These contrasting disease associations highlight ORAI2's context-dependent roles in cell-type-specific calcium signaling, with implications for both neuroprotection and cancer progression.