In October 2026, the biomedical community marks twenty years since the publication of the landmark paper by Takahashi and Yamanaka (2006), which first demonstrated that a differentiated cell could be induced to acquire a pluripotent state [1].

In the two decades since the first induced pluripotent stem cell (iPSC) colonies were obtained, somatic cell reprogramming has developed into an important experimental platform in both basic biology and medicine. iPSC-based systems are now used to model not only monogenic disorders but also complex multifactorial diseases. Their experimental potential has been further expanded by genome editing, single-cell sequencing technologies and the development of organoid models that reproduce selected aspects of organogenesis. More recently, differentiated derivatives of iPSCs have begun to enter the field of cell-based therapies and are being evaluated as biomedical cell products. Yet the historical importance of the original experiment remains difficult to overstate. Starting with 24 candidate genes, five six-well plates and only 22 surviving colonies, it led to a fundamentally new view of cellular plasticity. The work ultimately contributed to the 2012 Nobel Prize and laid the foundation for an entire area of regenerative medicine that is now moving into a more mature, clinically oriented phase. This review discusses the experimental developments that preceded the discovery of induced pluripotency, summarizes the major advances achieved over the following two decades, and considers the directions in which the field is likely to develop further.