NPC2 is a lysosomal cholesterol transporter essential for intracellular cholesterol homeostasis. It functions by accepting unesterified cholesterol released from LDL in late endosomes/lysosomes and transferring it to NPC1's N-terminal cholesterol-binding pocket in a 1:1 stoichiometric manner 12. Beyond cholesterol, NPC2 can bind diverse sterols including lathosterol, desmosterol, and plant sterols 1. The protein may also mobilize membrane-associated cholesterol 3, and its secreted form regulates biliary cholesterol secretion via ABCG5/ABCG8 stimulation. Dysfunction of NPC2 causes Niemann-Pick disease type C2 (NP-C2), an autosomal recessive lysosomal storage disorder affecting ~1/120,000 live births 4. Mutations in NPC2 account for approximately 5% of NP-C cases, the remainder involving NPC1 45. The disease manifests as a neurovisceral disorder with cholesterol and ganglioside accumulation in lysosomes, presenting with variable severity from neonatal lethality to adult-onset neurodegeneration characterized by ataxia, gaze palsy, and progressive dementia 46. Beyond genetic disease, NPC2 expression is upregulated in cancer cells to mobilize cholesterol for rapid membrane synthesis during tumor growth 7. Additionally, inhibition of NPC2 cholesterol binding can induce immunogenic cell death, offering potential cancer therapeutic opportunities 8.