Humans have two type IB topoisomerases (Top1 and Top1mt), and TOP1 is one of the six vertebrate topoisomerase genes (TOP1, TOP1MT, TOP2A, TOP2B, TOP3A and TOP3B). Topoisomerase activity is essential for transcription and a replication as DNA is an extremely long polymer (up to 2 meters in the nucleus of human cell) that readily forms loops, supercoils, knots and catenanes. Top1 autoantibodies are commonly found in the blood of patients with autoimmune diseases (Scleroderma pigmentosum). Top1 is generally overexpressed in cancer cells and the target of widely used camptothecin derivatives. Novel indenoisoquinoline Top1 inhibitors and targeted delivery Top1 inhibitors are in clinical trials.