THSD7B (thrombospondin type 1 domain containing 7B) is a protein involved in actin cytoskeleton organization and plasma membrane interactions. Genetically, THSD7B variants are associated with multiple addiction phenotypes, including alcohol dependence 1 and nicotine dependence 2, with evidence suggesting shared genetic architecture across substance addictions. In cancer biology, THSD7B exhibits context-dependent roles: mutations confer platinum resistance and poor prognosis in small cell lung cancer through inhibition of cell death pathways and downregulation of immune responses 3, while heterozygous mutations have been identified in familial lung adenocarcinoma 4. Conversely, exercise-induced upregulation of THSD7B correlates with tumor suppression and improved prognosis across multiple cancer types 5. THSD7B variants also associate with apolipoprotein A-II regulation during pregnancy 6 and exhibit differential methylation in oral leukoplakia 7. A novel NFIB::THSD7B fusion has been identified in lacrimal gland adenoid cystic carcinoma 8. Collectively, THSD7B represents a pleiotropic gene with implications for addiction susceptibility, cancer prognosis, and metabolic regulation, suggesting potential therapeutic targeting in specific disease contexts.