A novel TGFβ Inducible Early Gene-1 (TIEG1) was discovered in human osteoblast (OB) cells by our laboratory. Over the past decade, a handful of laboratories have revealed a multitude of organismic, cellular, and molecular functions of this gene. TIEG1 is now classified as a member of the 3 zinc finger family of Krüppel-like transcription factors (KLF10). Other closely related factors [TIEG2 (KLF11) and TIEG3/TIEG2b] have been reported and are briefly compared. As described in this review, TIEG1 is shown to play a role in regulating estrogen and TGFβ actions, the latter through the Smad signaling pathway. In both cases, TIEG1 acts as an inducer or repressor of gene transcription to enhance the TGFβ/Smad pathway, as well at other signaling pathways, to regulate cell proliferation, differentiation, and apoptosis. This review outlines TIEG1’s molecular functions and roles in skeletal disease (osteopenia/osteoporosis), heart disease (hypertrophic cardiomyopathy), and cancer (breast and prostate). J. Cell. Biochem. 102: 539–548, 2007.