TPCN2 encodes two-pore segment channel 2, a lysosomal Na+/Ca2+ ion channel that regulates intracellular calcium homeostasis and endosomal trafficking. The channel exhibits ligand-dependent selectivity, functioning as a NAADP-activated Ca2+ release channel or a PI(3,5)P2-activated Na+ channel depending on activation mode 1. TPCN2 is critical for coronavirus entry into host cells, with loss-of-function studies demonstrating its requirement for SARS-CoV, SARS-CoV-2, and HCoV-EMC endocytosis 2. Beyond viral pathogenesis, TPCN2 regulates autophagy progression and extracellular vesicle trafficking in cancer cells; overexpression inhibits autophagosome-lysosome fusion while knockdown enhances cell migration 3. TPCN2 dysfunction contributes to multiple diseases: it is downregulated in heart failure from both ischemic and dilated cardiomyopathy, implicating mitochondrial quality control defects 4, and genetic variants associate with aortic stenosis risk independent of coronary artery disease 5. In Parkinson's disease, the LRRK2 G2019S mutation exaggerates calcium entry through disrupted lysosomal TPC2 function, with selective TPC2 inhibition or biased agonism reversing pathological phenotypes 6. These findings establish TPCN2 as a multi-functional ion channel with therapeutic potential across infectious, cardiac, and neurological diseases.