The H syndrome is a recently described autosomal recessive genodermatosis with several systemic manifestations. The name derives from its major clinical and laboratory findings, which comprise cutaneous hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, hyperglycemia/diabetes mellitus, low height, hallux valgus and fixed flexion contractures of the toe and proximal interphalangeal joints. However, the main characteristic of the disease is hypertrichosis with hyperpigmentation, which localize mainly to the thighs and shins. Homozygosity mapping and further sequencing revealed various mutations (missense, compound and deletion) in the SLC29A3 gene, which encodes the widely expressed equilibrative nucleoside transporter; hENT3, that localizes to the mitochondria. Recently, it was found that knockdown of the gene encoding the hENT3 drosophila ortholog led to ectopic bristle induction, similar to the hypertrichosis phenotype observed in syndrome H patients. These findings suggest that hENT3 is a major regulator of hair growth and pigmentation, and invite further studies to better lineate the role of nucleotide transporters and mitochondria in the hair follicle, and promise to serve as a novel target for treating hair and pigmentary diseases.