The regulation of gene expression plays an important role not only during embryonic development but also in the course of cell differentiation and regeneration processes of various tissues, e.g. skeletal muscles, intestines, or nerves. Tightly regulated gene expression in particular cell types requires a sophisticated interplay between the basic transcriptional machinery and specific transcriptional regulators--activators, repressors, co-activators, and co-repressors. The last category includes the TPA Induced Sequence 7 (TIS7) protein family, recently characterized as transcriptional co-repressors. The expression of these proteins is regulated on the mRNA level and directly correlates with the processes of cell and tissue differentiation not only during embryonic development but mainly throughout the regeneration events in adult organisms. The expression of TIS7 and its homologue SKMc15 is ubiquitous and according to current knowledge, as summarized in this review, TIS7 plays a role in the differentiation of various cell types, e.g. epithelial cells, myoblasts, hematopoietic cells, or neurons. Here, we not only focus on the description of TIS7 expression in various systems (species, organs) but also try to provide current state of knowledge of the regulatory mechanisms in which TIS7 is involved. The clarification of biochemical mechanisms directed by the TIS7 family members during regeneration events, e.g. following injury, will additionally provide us with the opportunity to intervene therapeutically.