TMC8 is a transmembrane regulatory protein that functions primarily in zinc homeostasis and immune regulation. In keratynocytes and lymphocytes, TMC8 forms a complex with its homolog TMC6 and calcium-binding protein CIB1, wherein TMC6 and TMC8 stabilize CIB1 levels 12. Together with TMC6, TMC8 activates zinc transporter ZNT1 at the ER membrane, facilitating zinc uptake into the endoplasmic reticulum 3. Additionally, TMC8 inhibits receptor-mediated calcium release and suppresses activity of zinc- and cytokine-induced transcription factors 3. TMC8 also sequesters TRADD protein, impairing TNF-induced survival signaling and promoting apoptosis 4. Clinically, TMC8 mutations cause epidermodysplasia verruciformis (EV), a rare autosomal recessive disorder characterized by abnormal susceptibility to cutaneous human papillomavirus (HPV) infection 56. EV patients develop persistent plane warts and have significantly elevated risk for cutaneous squamous cell carcinoma, particularly in UV-exposed regions 5. In head and neck squamous cell cancer, TMC8 upregulation correlates with improved prognosis and is associated with enhanced CD4+ T cell infiltration, suggesting TMC8 promotes anti-HPV immunity 7. Recent evidence indicates that TMC6/8 deficiency causes a subtle cellular immune deficit rather than acting as intracellular viral restriction factors 8, explaining the immunological basis of typical EV susceptibility to β-HPV infection.