SLC29A3 encodes equilibrative nucleoside transporter 3 (ENT3), a uniporter that facilitates nucleoside transport across lysosomal and mitochondrial membranes 123. The transporter functions as a non-electrogenic, Na+-independent system with pH-dependent activity enhanced under acidic conditions, reflecting its localization in acidic intracellular compartments 123. ENT3 transports various nucleosides (adenosine, guanosine, uridine, thymidine, cytidine, inosine), deoxynucleosides, nucleobases, and monoamine neurotransmitters, facilitating salvage synthesis of nucleic acids 1243. Loss-of-function mutations in SLC29A3 cause lysosomal nucleoside storage, leading to histiocytosis through TLR7/8-mediated stress responses that drive phagocyte proliferation and accumulation in multiple organs 5. These mutations are associated with H syndrome and related disorders including dysosteosclerosis, Faisalabad histiocytosis, and pigmented hypertrichosis with insulin-dependent diabetes 678. The clinical spectrum includes cutaneous hyperpigmentation, hypertrichosis, skeletal abnormalities, diabetes, and multisystemic involvement 910. ENT3 dysfunction also impacts cancer progression and chemotherapy efficacy, making it a potential therapeutic target 11.