MR analysis identified SHISA5 as a causal risk gene for thyroid cancer, and molecular docking revealed strong binding affinity with acetaminophen, suggesting therapeutic potential.<h4>Conclusions</h4>PTC-blank and PTC-thyroiditis exhibit distinct LNM mechanisms: ECM remodeling and fibroblast infiltration are associated with metastasis in PTC-blank, while immune dysregulation appears to be more prominent in PTC-thyroiditis. Here, SHISA5 is linked to thyroid gland disorder.